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Purpose: To determine the efficacy and safety of cryoablation in pediatric and young adult patients with desmoid tumors (DTs) retrospectively over a 10-year period., Materials and Methods: Twenty-one patients (age 2-22 years; median 14 years), with 21 desmoid tumors, underwent a total of 34 percutaneous cryoablation procedures between August 2013 and August 2023. All patients, excluding two, had surgical resection, chemotherapy, or a combination of these therapies with failed or suboptimal response. Clinical and imaging outcomes were analyzed for technical success, change in tumor volume, and recurrence of tumor, symptom improvement or recurrence, and procedure-related complications., Results: All procedures were technically successful. The median follow-up duration was 9 months (range, 3-32 months); total symptomatic improvement was achieved in 90% (19/21) patients, noticeable pain relief was seen in 100% (18/18) and 90% (9/10) patients had improved range of motion (ROM), discomfort resolved in 66.7% (2/3) patients. Of the treated tumors, 43% (9/21) showed greater than 75% tumor volume reduction of which 44% (4/9) had no evidence of viable residual tumor at follow-up, and 33% (7/21) had 50-75% volume reduction and 14% (3/21) had greater than 40-50% tumor volume reduction. According to modified response evaluation criteria in solid tumors (mRECIST), 71%( 15/21) had partial response (PR), 19% (4/21) had complete response (CR), and 10% (2/21) had stable disease. Four (12%) treatments were associated with minor complications, which self-resolved., Conclusion: In this, predominantly pediatric patient cohort, cryoablation was effective and safe for the local control of extra-abdominal desmoid tumors in short-term follow-up., (© 2024. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

When evaluating pediatric patients of color, it is essential to consider the unique diagnostic and treatment factors that apply to this population. Certain dermatologic conditions are more common in these patients, including postinflammatory hyperpigmentation, pityriasis alba, progressive macular hypomelanosis, tinea capitis, traction alopecia, keloids, hypertrophic scars, pseudofolliculitis barbae, acne keloidalis nuchae, and hidradenitis suppurativa. Furthermore, conditions such as vitiligo are more noticeable in people of color. This can lead to a significantly diminished quality of life, so these conditions should be quickly recognized and treated. Notably, inflammation can be difficult to recognize on the skin of people of color, which can lead to the underestimation of severity as well as inappropriate treatment. Treatment recommendations can also differ based on lifestyle or cultural norms, such as the use of tinted sunscreens and the consideration of hair care practices. Pediatricians should be aware of these conditions and treatment considerations to best treat pediatric patients of color. [ Pediatr Ann . 2024;53(4):e146-e151.] .

Introduction : Aluminum phosphide is a pesticide that is used in developing countries. Aluminum phosphide poisoning has a high mortality rate and there is no known antidote. This study aimed to evaluate the safety and efficacy of insulin-euglycemia therapy in the management of patients with acute aluminum phosphide poisoning. Methods : This trial was prospectively registered in the Pan African Clinical Trials Registry (PACTR202008534546951). A total of 108 patients were randomly allocated to two groups. The intervention group received insulin-euglycemia therapy in addition to standard treatment (norepinephrine and supportive care); the control group received standard treatment plus placebo. The main outcome measures were survival, blood pressure, and laboratory investigations. Results : The two groups had similar baseline parameters. Insulin-euglycemia therapy was associated with a significant reduction in mortality compared with that in the control group (64.8 percent and 96.3 percent, respectively; P value <0.001). Patients randomized to insulin-euglycemia also required lower doses of vasopressors (median was 7 mg versus 26 mg in control group; P value 0.006) and fewer patients needed intubation (61.1 percent versus 81.5 percent in the control group; P value 0.019). Insulin-euglycemia therapy significantly improved blood pressure (systolic, diastolic, and mean arterial pressure) (median at 6h post-admission was 80 mmHg, 55 mmHg and 65 mmHg compared with 20 mmHg, 10 mmHg and 13 mmHg in the control group respectively; P value <0.001) and bicarbonate and lactate concentrations. Conclusion : Insulin-euglycemia therapy appears to be a safe and effective treatment option for patients with aluminum phosphide poisoning. Vasopressor only therapy was associated with very poor outcomes in acute aluminum phosphide poisoning.

Purpose: To evaluate complications associated with cryoablation in a pediatric population and review preventive measures to mitigate these complications., Material and Methods: Retrospective study including all the image guided cryoablations performed on pediatric population. Immediate and delayed complications were analyzed, and we identified the different protective measures used and the clinical outcomes from follow-up. Point estimates for the percentage of complications were calculated by maximum likelihood, and 95% confidence intervals for the true percentages were calculated using the Clopper-Pearson exact method., Results: Eighty-seven ablations were performed on 68 patients (age range of 2-18 years, mean 12.4 years) for non-neoplastic (70%) and neoplastic (30%) lesions. The percentage of ablations resulting in complications was 18% (95% confidence interval (CI) 11% to 28%). Of these, 5% (95% CI 1% to 11%) were grade 3 complications, and 14% (95% CI 7% to 23%) were grade 2 complications. Thermal protection was performed in 27.6% of ablations (n = 24). The mean clinical follow-up duration was 348 days., Conclusion: Cryoablation in pediatric patients is relatively safe, with a major complication rate per ablation of 5%. Thermal protective measures can be considered to mitigate these complications., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature and the Cardiovascular and Interventional Radiological Society of Europe (CIRSE).)

Purpose: To assess the safety and efficacy of the posthemostasis use of an inflatable adhesive external compression device (SafeGuard) following angiography in children performed under general anesthesia., Materials and Methods: Medical records of 74 children (43 females) with a mean age of 8.9 years (range, 0.4-18.0 years) and mean weight of 44.0 kg (range, 7.3-115.7 kg) in whom an inflatable adhesive external compression device was used for maintaining hemostasis following angiography under general anesthesia were retrospectively reviewed. After establishing hemostasis with manual compression, the device was applied and inflated over the arteriotomy. The patients were assessed for access-related adverse events in the recovery unit and during postprocedural follow-up., Results: The inflatable adhesive external compression device was utilized to maintain hemostasis following 181 angiography procedures. The mean length of the procedure was 396 minutes. The common femoral artery (n = 170, 93.9%) was the most common access, using 4-5-F vascular sheath (n = 118, 65.2%) or 3-5-F sheathless (n = 8, 12.7%) catheters. The mean time to deflation was 93 minutes. There were no adverse events other than minor bleeding from the arteriotomy after deflation (n = 2, 1.1%) and early deflation of the device because of pain (n = 1, <1%). Follow-up ultrasonography (n = 109 procedures, 60.2% at a mean follow-up of 2.2 years) demonstrated patency of the access artery., Conclusions: The use of an inflatable adhesive external compression device following angiography in children to maintain hemostasis during the emergence phase of anesthesia and recovery period is safe and effective. The use of this simple device may reduce the need for postprocedural sedation and facilitate early discharge., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Clinical manifestations of blue rubber bleb nevus syndrome (BRBNS) and multifocal venous malformation (MVM) vary depending on the location of the lesions. The aim of this study was to assess the risk of developing CSF leaks in patients with epidural venous malformations (VMs)., Methods: The authors retrospectively investigated the relationship between the development of a CSF leak and the presence of epidural VMs., Results: Nine patients (5 females) had epidural VMs and presentation that was confirmatory or suggestive of a CSF leak: 4 had BRBNS, 4 had MVMs, and 1 had a solitary VM. Of 66 patients with BRBNS, clinical and imaging features of CSF leak were noted in 3 (4.5%) with epidural VMs at the age of 11-44 years. A fourth patient had suggestive symptoms without imaging confirmation. An epidural blood patch was ineffective in 2 patients, both with more than one source of leakage, requiring surgical repair or decompression. Symptomatic downward displacement of the cerebellar tonsils was noted in 3 patients with MVM and 1 with a solitary VM; 3 required surgical decompression., Conclusions: These findings suggest an increased risk of CSF leak in patients with epidural VM, including BRBNS, MVMs, and solitary VMs. Awareness of the association between epidural VM and CSF leakage may facilitate earlier diagnosis and therapeutic intervention.

Dialysis treatment for chronic kidney disease was first developed by Dr. Willem Kolff in 1943, and its availability began to grow in 1962 after which it has become a mainstay treatment for patients with chronic kidney disease. It is estimated that, in 2021, 15% of adults in the United States (∼37 million people) have chronic kidney disease, of which 661,000 individuals have renal failure, and 468,000 individuals require dialysis. There have been several advancements in dialysis treatment since its advent, most notably the creation of arteriovenous fistulas (AVFs) for venous access in 1966. In recent years, the U.S. Food and Drug Administration approved two new devices for AVF creation using a percutaneous approach. These are the WavelinQ (Becton Dickinson, New Jersey) and the Ellipsys (Avenu Medical, California) endovascular AVF (endoAVF) devices that use radiofrequency and thermal technologies, respectively, to create the AVF. Since the introduction of these technologies, several studies have shown that they are safe and effective, with favorable durability and low rate of serious adverse events. In this article, we will discuss these two devices and the techniques used for percutaneous creation of dialysis AVF as an alternative to traditional open surgical techniques., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Purpose: To describe the use of the internal mammary vein as an alternative access for central venous catheters., Methods: We performed a retrospective review of patients who underwent placement of central venous catheters via the internal mammary vein. Patient demographics, indication for venous access, technical success, catheter type, dwell time and indication for exchange or removal were recorded., Results: Placement of central venous catheters via the internal mammary vein was attempted in 11 patients including 8 children (4 males, mean age 5.7 years) and 3 adults. The most common indication was parenteral nutrition in patients with intestinal failure (7/11). Initial needle access of the vein was successful in all patients. Catheter placement was successful in 9 and unsuccessful in 2 patients due to occlusion of the superior vena cava. There were no immediate complications. A total of 20 catheters of various sizes (3-14.5 French) and lengths (8-23 cm) were either placed (n = 12) or exchanged (n = 8). The most common indications for catheter exchange were poor function and malposition (7/8). Four catheters were removed for infection and 4 were accidentally removed. The mean dwell time was 141 days (range 0-963 days) per catheter for a total of 2829 catheter days. The total mean dwell time per patient, including primarily placed and exchanged catheters, was 314 days (range 5-963 days)., Conclusions: The internal mammary vein may provide a safe alternative route for patients who have lost their traditional access veins., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aim: To describe and analyze the demographic characteristics and to determine the angiographic features of acute central serous chorioretinopathy(CSCR) in an Egyptian population., Methods: A series of consecutive patients presenting with acute idiopathic CSCR to Mansoura Ophthalmology Center Mansoura University who underwent fluorescein angiography (FA) within a 3-year-period (between January 1, 2007 and December 31, 2009) was retrospectively studied. Patient demographics and angiographic features were studied. Results were compared to those of other Western and Asian populations., Results: Fluorescein angiograms of 86 patients were analyzed. 91% were males. The age range of patients was 24 - 49 years, with a mean age of (38±6) years. The right eye was the presenting eye in 47% of patients. Eighty-seven percent of eyes showed delayed choroidal filling. Thirty-five percent of patients had more than one point of leakage. The macula was the most common site of fluorescein leakage seen in 79% of patients. Peripheral leakage was seen in 14% of patients while peripapillary leakage was seen in 12% of patients. The inkblot leakage pattern was found in 53% of patients. The presenting eye had RPE atrophic changes in 84% of cases. The other eye was assessed in 44 patients (51%). Fifty-five percent of them had signs of RPE atrophic changes., Conclusion: In the Egyptian population, CSCR is seen at younger age with higher male-to-female ratio and more frequent smokestack leaks than other populations. Despite younger age group, this series of patient showed higher frequency of bilateral and multifocal disease compared to other studies. Roles of psychological stress and choroidal ischemia in pathogenesis of CSCR need further evaluation.

Background and Objective: To evaluate the safety and efficacy of intraoperative subconjunctival bevacizumab as an adjunctive treatment after surgical excision of primary pterygium., Patients and Methods: This was a randomized prospective clinical study. Group 1 (21 eyes) underwent pterygium excision with conjunctivo-limbal autograft. Group 2 (20 eyes) received subconjunctival 1.25 mg/0.05 mL of bevacizumab at the end of the surgery., Results: There were no statistically significant differences regarding age, sex, laterality, or dimensions of the pterygia or grafts between the two groups (P > .05, 95% confidence interval). After 8 months of follow-up, two eyes in group 1 and four eyes in group 2 had recurrent pterygia. One patient in group 2 had lost graft. The difference in recurrence rate between the two groups did not reach statistical significance (P = 0.4, 95% confidence interval)., Conclusion: Intraoperative subconjunctival bevacizumab following primary pterygium surgical excision is not helpful and possibly harmful. Larger studies are needed., (Copyright 2012, SLACK Incorporated.)

Purpose: To compare the efficacy and safety of intravitreal diclofenac versus intravitreal triamcinolone acetonide in the treatment of diabetic macular edema., Methods: Thirty-two eyes with diffuse diabetic macular edema were randomly allocated to intravitreal injection of 4 mg/0.1 mL of triamcinolone (Group 1: N = 16) or 500 μg/0.1 mL of diclofenac (Group 2: N = 16). Preoperative and postoperative visual acuity, intraocular pressure, and central macular thickness were recorded and compared between the 2 groups up to 12 weeks., Results: Both groups showed statistically significant reduction in central macular thickness (triamcinolone: P = 0.02 and diclofenac: P = 0.01), without statistically significant difference between the 2 groups. Visual improvement was significant only in triamcinolone group (P = 0.05). However, the 2 groups showed no statistically significant difference in mean visual acuity or mean line improvement. Transient elevation of intraocular pressure occurred in 12.5% of the triamcinolone group. Diclofenac group showed statistically significant reduced intraocular pressure (P = 0.02)., Conclusion: Intravitreal diclofenac is effective in the treatment of diffuse diabetic macular edema up to 12 weeks. Intravitreal triamcinolone and diclofenac appear to have comparable therapeutic effects on retinal thickness. The degree of visual improvement is higher with triamcinolone.

Purpose: To compare the functional and anatomical outcomes following intravitreal triamcinolone acetonide vs. intravitreal bevacizumab (Avastin) treatment for diffuse diabetic macular edema., Materials and Methods: IN THIS PROSPECTIVE, RANDOMIZED STUDY, SUBJECTS WERE DIVIDED INTO TWO GROUPS: 24 eyes that received intravitreal injection of 4 mg/0.1 mL triamcinolone acetonide (IVTA group) and 24 eyes received intravitreal injection of 1.25 mg/0.05 mL bevacizumab (IVB group). Changes in best corrected visual acuity (BCVA), intraocular pressure (IOP), baseline fluorescein angiography and optical coherence tomography measurements were evaluated in both groups. Follow-up visits out to three months from baseline are reported., Results: One month after treatment, baseline foveal thickness decreased from 452 µ to 299 µ in the IVTA group and from 292 µ to 270 µ in the IVB group. BCVA increased by two or more lines in 58.3% of eyes in the IVTA group and there was no similar improvement in the IVB group. In the IVTA group, a transient increase in IOP (27-43 mmHg) occurred in four cases (16.7%), which was successfully controlled with topical medications. There were no complications in the IVB group., Conclusion: Short term outcomes indicate that intravitreal injection of bevacizumab was not associated with surgical complications compared to triamcinolone acetonide. Triamcinolone acetonide appears to be more effective treatment for diabetic macular edema than bevacizumab.

Purpose: To evaluate absolute filling defects of the optic disc and color Doppler imaging (CDI) measurements in primary open angle glaucoma (POAG) to assess their diagnostic potentialities., Methods: Twenty patients with POAG and 20 age- and sex-matched controls were included in this study. Fluorescein angiograms were performed and percentage of absolute fluorescein filling defects was calculated. Peak systolic velocity (PSV), end diastolic velocity (EDV), and resistive indices (RI) of the ophthalmic artery (OA), central retinal artery (CRA), and temporal and nasal short posterior ciliary arteries (TPCA, NPCA) were measured using CDI., Results: Absolute filling defects of the optic nerve head and RI of CRA were significantly larger in patients with POAG (p<0.001). EDV of CRA, TPCA, and NPCA were significantly reduced in POAG (p<0.05). RI of OA, TPCA, and NPCA were significantly increased in patients with POAG (p<0.05). Absolute fluorescein filling defects percentages correlated with the RI of CRA and NPCA. They correlated negatively with EDV of CRA, NPCA, and TPCA. The diagnostic accuracy of the RI of CRA in glaucoma was 96% while that of absolute fluorescein filling defects percentages was 92%., Conclusions: The combination of different techniques allows further interpretation of ocular circulatory changes in glaucoma and help in diagnosis of glaucoma. Further studies are needed for better understanding of the relationship between circulatory and neural loss.

Possible tumor-promoting activity of four flavonoids, quercetin (QC), tangeretin (TG), flavone (FO), and flavanone (FN), was examined in a rat liver short-term carcinogenesis assay as well as with in vivo and in vitro assays of inhibition of gap junctional intercellular communication (GJIC). Rat hepatocarcinogenesis was induced by aflatoxin B1 treatment followed by a selection phase (2-acetylaminofluorene treatment and partial hepatectomy), then treatment with or without test chemicals (in vivo studies of antipromotion were not performed). Using glutathione S-transferase placental form (GST-P)-positive foci, we compared the effects of flavonoids (at 1,000 ppm in the diet) with the effects of phenobarbital (PB) on the occurrence of liver preneoplastic lesions. In addition, we studied the effects of flavonoids on GJIC in the livers derived from these experiments and in two types of cultured cells. No significant difference in the number and area of GST-P-positive foci was found after one or three months of treatment between any flavonoid group and control group. In the positive control group, PB markedly increased the numbers and areas of preneoplastic lesions at three months. Whereas PB also decreased by 60% the average size of lucifer yellow dye spread in slices of liver parenchyma free of preneoplastic lesions among the different flavonoids, only TG decreased the dye transfer in vivo: by 30% at one month and 50% at three months. With the dye transfer assay applied to a rat liver epithelial cell line (REL) and the Chinese hamster V79 metabolic cooperation assay, none of the tested flavonoids (< or = 25 microM) inhibited GJIC. Conversely, protective properties were seen for some of the compounds in antipromotion in vitro studies, because TG and FN enhanced the dye transfer in REL cells and FO, TG, and QC partly prevented the inhibition of metabolic cooperation by 12-O-tetradecanoylphorbol-13-acetate. Thus, taken together, our results suggest that QC, FO, and FN do not show tumor-promoting activity. Concerning TG, some discrepancies in the in vivo data are observed. Some of them (GJIC inhibition in liver slices) are probably more relevant to promotion of hepatocarcinogenesis.

The mutagenicity of 20 p-phenylenediamine derivatives has been investigated in Salmonella typhimurium. Tests were performed in the presence and in the absence of Aroclor 1254-induced liver S9 fractions derived from male Wistar rats. Among five series of compounds tested, nitro-p-phenylenediamines with substituents at the C6 position (4-amino-3-nitro-6-methylaniline; 4-amino-3-nitro-6-methoxyaniline; 4-amino-3-nitro-6-fluoroaniline; 4-amino-3-nitro-6-chloroaniline; and 4-amino-3-nitro-isopropylaniline) were the most mutagenic. In all cases, the compounds were less mutagenic in the absence of S9 than in its presence, but three of the five compounds (the methoxy, fluoro, and chloro derivatives) were still mutagenic without the metabolic activation system. In contrast to the mutagenicity of the C6-substituted compounds, the mutagenicity of analogues with substituents on the C5 position (4-amino-3-nitro-5-beta-hydroxypropylaniline; 4-amino-3-nitro-5-isopropylaniline; 4-amino-3-nitro-5-methylaniline; and 4-amino-3-nitro-5-beta-hydroxyethylaniline) was abolished or reduced. A dramatic reduction in mutagenic activity was also achieved when two methyl groups, instead of one, were added to 4-amino-3-nitroaniline. For example, 4-amino-3-nitro-5,6-dimethylaniline and 4-amino-3-nitro-2,5-dimethylaniline were only weakly mutagenic, and 4-amino-3-nitro-2,6-dimethylaniline as 4-amino-2-6-dimethylaniline; 4-amino-5,6-dimethylaniline; was nonmutagenic. Monocyclic compounds such as 4-amino-2,6-dimethylaniline; 4-amino-5,6-dimethylaniline; 4-amino-2-methoxy-3,5-dimethylaniline, and 4-amino-2,3,5,6-tetramethylaniline were all nonmutagenic in Salmonella typhimurium. The compound 4-amino-2,5-dimethylaniline was weakly mutagenic or nonmutagenic, whereas 4-amino-2,5-dimethoxyaniline was mutagenic. It appears that the mutagenic activity or inactivity of these compounds depends on both the chemical groups present and their positions in the molecule. In this context, it seems that the presence of the NO2 group and the nature of the substituent groups at the C5 and C6 positions on the benzene ring are crucial factors in determining the mutagenicity of these compounds.

The effects of retinoic acid and retinol acetate on gap junctional communication were examined in two in vitro tests. Rat liver epithelial cell line IAR 203 was used for dye transfer assays, and hamster lung fibroblast V79 cells were used for metabolic cooperation assays. A reversible dose-dependent inhibition of dye transfer was detected after a 1-hr treatment with retinoic acid or retinol acetate at concentrations ranging from 10 to 50 microM. On the other hand, enhancement of dye transfer was observed after a 24-hr treatment with retinoic acid at 0.1 microM. A dose-dependent inhibition of metabolic cooperation was obtained with retinoic acid at noncytotoxic concentrations ranging from 5 to 50 microM. Retinoids and TPA (1 ng/ml) acted synergistically in their inhibition of cell communication. Thus, the assays appear to be complementary: the dye transfer assay was useful in studying the time course and the reversibility of the inhibition or enhancement of dye transfer, whereas the metabolic cooperation assay was effective in quantifying the inhibitory effect of TPA or retinoids and interactions between them.

Studies were conducted to explore structure-activity relationships for 4'-N,N-dimethylamino-1'-phenylazo-3-pyridine and nine structurally related compounds in Salmonella typhimurium tester strains TA1535, TA100, TA1537, TA1538, TA98. Each compound was tested for mutagenicity at five or more concentrations that varied from 10-5000 micrograms/plate. We used the standard plate test and the investigations were carried out both in the absence and presence of Aroclor-1254-induced rat-liver homogenate and the components of the NADPH-generating system. Negative response was observed for 4'-N,N-dimethylamino-1'-phenylazo-3-pyridine and five of its analogues (4'-N,N-diethylamino-1' phenylazo-3-pyridine; 4'-N,N-di-(beta-hydroxyethylamino)-1' phenylazo-3-pyridine; 4'-N-methylamino sulfonic acid-1'-phenylazo-3-pyridine; 4'-N,N-dimethylamino-6'-acetamido-1' phenylazo-3-pyridine, and 4'-N,N-di-(beta-hydroxyethylamino)-6'-methyl-l' phenylazo-3-pyridine). When S9 induced by Aroclor-1254 was present, the compound 4'-N,N-dimethylamino-6-methoxy-1' phenylazo-3-pyridine exhibited mutagenic activity in the two strains TA1538 and TA98. The compound 4',6'-diamino-3-methyl-1'-phenylazo-3-pyridine was also mutagenic, both in the presence and in the absence of S9 mix. The two compounds 4'-N,N-dimethylamino-6-butoxy-1'-phenylazo-3-pyridine and 4'N,N-di-(beta-hydroxyethylamino)-1'-phenylazo-3-[6-N,N-di-(beta- hydroxyethylamino) pyridine were either weakly mutagenic or nonmutagenic. On the basis of these data, it is concluded that the mutagenicity of phenylazo-3-pyridines, like monocyclic aromatic amines and azo dyes, is influenced by the nature of the substituent chemical groups and their positions in the molecular structure of the compounds.

Effects of p-aminobenzoic acid (PABA) and of 4-[(2-oxo-3-bornylidene)methyl]-phenyl trimethylammonium methylsulfate (OMM), two components used in sunscreen formulations, on the mutagenicity of UVB irradiation are compared in three genetic assay systems. A haploid strain of Saccharomyces cerevisiae XV185-14C was used to measure reverse mutations at three loci. The diploid strain D5 of Saccharomyces cerevisiae was used to screen for reciprocal mitotic recombination. The induction of forward mutations was measured in Chinese hamster V79 cells. Our results indicate that UVB irradiation induced HGPRT- mutants in V79 cells, reverse mutations in Saccharomyces cerevisiae strain XV185-14C, and mitotic crossing over and other genetic alterations in Saccharomyces cerevisiae strain D5. V79 Chinese hamster lung cells were the most sensitive to UVB irradiation, followed by Saccharomyces cerevisiae haploid strain XV185-14C and the diploid strain D5. PABA and OMM were both capable of protecting all three types of cells from UVB irradiation regarding both lethality and induction of various types of genetic alterations. At higher concentrations (above 10(-5) M), OMM was more effective in its photoprotective effect toward UVB irradiation than PABA.

Genetic effects of UV-A, UV-B, UV-C, and the combination of 8-methoxypsoralen (8-MOP) with UV-A or visible light were studied in the haploid strain XV185-14C and diploid strain D5 of Saccharomyces cerevisiae. The induction of his+, lys+, and hom+ reverse mutations was measured in strain XV185-14C. In strain D5 we measured the induction of genetically altered colonies, particularly twin spot colonies arising from a mitotic crossing-over. UV-C and UV-B induced point mutations at the three loci in the haploid strain and mitotic crossing-over and other genetic alterations in the diploid strain. UV-C was more mutagenic and recombinogenic than UV-B. UV-A or visible light alone did not induce genotoxic effects at the doses tested. However, UV-A plus 8-MOP produced lethal and mutagenic effects in the haploid strain XV185-14C, although mutagenic activity was less than that of UV-B. Visible light plus 8-MOP also induced genotoxic effects in strain XV185-14C. In the diploid strain D5, UV-A plus 8-MOP induced a higher frequency of genetic alterations than UV-B at comparative doses. Visible light plus 8-MOP was also genetically active in strain D5. The haploid strain was more sensitive to the lethal effects of UV-C, UV-B, UV-A, and impure visible light plus 8-MOP than the diploid strain.

Synopsis The mutagenicity of aniline was investigated in association with norharman using Aroclor 1254-induced and uninduced liver S9 fractions. The non-mutagenicity of aniline in the Salmonella/mammalian microsome test was also re-examined under various experimental conditions. Aniline caused no increase in the number of revertants per plate in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98 at concentrations of up to 5000 mug/plate. S9 preparations from rat liver, hamster liver, rat spleen, or hamster spleen were all ineffective in activating aniline to a mutagen in tests using various concentrations of S9 in S9 mix. In contrast to the results with aniline alone, mixtures of aniline and norharman were mutagenic in strain TA1538 in the presence of S9 fractions from liver of rats pretreated with Aroclor 1254. The observed mutagenicity decreased as a function of the concentration of S9 in S9 mix. In the presence of uninduced liver S9 preparations, the mutagenicity of the mixture of the two compounds was slight (three-fold).

The related monocyclic aromatic amines 2,4-diaminoanisole (DAA), 2,4-diaminopropoxybenzene (DAPB) and 2,4-diaminobutoxybenzene (DABB) were tested for mutagenic activity in Salmonella typhimurium strain TA 1538, using S-9 fractions from livers, kidneys and spleens of male Wistar rats for metabolic activation. In the presence of an uninduced liver S-9 fraction, DAA was weakly mutagenic (a two- or threefold increase), and the other compounds were negative. Uninduced S-9 preparations from kidney, spleen or a mixture of kidney, spleen and liver homogenates did not activate any of the compounds. On the other hand, S-9 fractions from rat liver induced with Aroclor 1254 or with a combination of phenobarbital and 5,6-benzoflavone activated both DAA and DAPB, DAA being by far the more mutagenic of the two. S-9 preparations from mixed liver, kidney and spleen homogenates from animals pretreated with Aroclor or with phenobarbital and 5,6-benzoflavone were less effective than the liver homogenates. Aroclor-induced S-9 fractions from kidneys slightly activated DAA, but S-9 fractions from spleen were ineffective in all cases. The mutagenicity ranking of the aromatic amines was DAA greater than DAPB greater than DABB. The latter compound caused little or no increase over the control numbers of revertant colonies. The order of effectiveness of inducers was Aroclor 1254 greater than phenobarbital + 5,6-benzoflavone greater than no inducer, and that of preparations from different organs was liver greater than mixture of liver, kidney and spleen greater than kidney greater than spleen.

Synopsis In our studies of structure-activity relationships, four aminonitrophenol isomers and eleven derivatives of 3-amino-4-nitrophenol and 4-amino-3-nitrophenol were tested for their ability to induce mutations in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98. In the presence of an Aroclor-1254-induced rat-liver microsomal activation system (S9mix), 4-N-beta-hydroxyethylamino-3-nitroanisole and (4-amino-3-nitro) phenoxyethanol were mutagenic in several of these strains. The compounds 3-amino-4-nitrophenol, 3-N-methylamino-4-nitrophenol, 3-N-beta-hydroxyethylamino-4-nitrophenol, 3-amino-4-nitroanisole, 3-N-methylamino-4-nitroanisole, 3-N-beta-hydroxyethylamino-4-nitroanisole, (3-amino-4-nitro)phenoxyethanol, (3-methylamino-4-nitro)phenoxyethanol, (3-N-beta-hydroxyethylamino-4-nitro)phenoxyethanol, 4-amino-3-nitrophenol and 4-N-beta-hydroxyethylamino-3-nitrophenol were inactive, both in the presence and in the absence of S9 mix. In contrast to the results with 3-amino-4-nitrophenol and 4-amino-3-nitrophenol, which were negative, the isomers 2-amino-4-nitrophenol and 2-amino-5-nitrophenol were found to be mutagenic. These results on mutagenic and non-mutagenic aminonitrophenols and their derivatives suggest that the occurrence of mutagenic activity among these compounds depends on the nature of the substituent chemical groups and their position in the molecular structure of the compounds.

The hair-dye coupler resorcinol and the oxidation product of p-phenylenediamine d resorcinol, hydroxy-3-(p-amino)anilino-6,N-[(p-amino)phenol]benzoquinonemonoimine-1.4, were tested for mutagenicity in the histidine-requiring mutants of Salmonella typhimurium (TA100, TA1535, TA1537, TA1538 and TA98). The investigations were carried out in the absence and presence of rat-liver homogenate induced by Aroclor 1254 and the components of the NADPH-generating system. There was no indication of mutagenic activity by these 2 compounds at any of the 8 concentrations used. The nuclear magnetic resonance spectrum of the reaction product of p-phenylenediamine and resorcinol was recorded and is in agreement with its chemical structure.

The mutagenicity of six monocyclic aromatic amines (2,4-diaminoanisole, 2,4-diaminoethoxybenzene, 2,4-diaminopropoxybenzene, m-phenylenediamine, 2,4-diaminotoluene, and nitro-p-phenylenediamine) was investigated in Salmonella typhimurium strains TA97, TA1537, and TA1538 in the presence of two different amounts of Aroclor 1254-induced S9 preparations. Strain TA1538 was found to be the most responsive of the three strains with this group of compounds. Regarding the other strains, TA1537 responded to three of the compounds better than strain TA97, if one calculates responsiveness as the fold-increase in numbers of revertants per plate. However, if one calculates the number of revertants per nanomole or compares the number of induced revertants per plate, TA97 was more responsive than TA1537 for all six compounds. Comparisons of mutagenesis from tests involving strain TA97 are complicated by the large variations in spontaneous mutation frequencies in this strain. The amount of S9 per plate is another important variable in tests of monocyclic aromatic amines; in general, more revertants are detected when the S9 mix contains 10% S9 than when it contains 4% S9. Nevertheless, in all our tests of 2,4-diaminoanisole, 2,4-diaminoethoxybenzene, and 2,4-diaminopropoxybenzene, the same relationship between chemical structure and mutagenic activity was observed. In all three strains, the mutagenic responses become less when the alkoxy substituent on the molecule becomes larger.

Niridazole, one of several drugs presently known to be of value in the treatment of human schistosomiasis, was tested for its activity in inducing mitotic recombination in yeast. It was found that niridazole is genetically active when the treatment of yeast cells is performed in a rich medium (YPG-medium) under growing conditions, but not when treatment is carried out in a non-nutrient suspension (phosphate buffer). The data suggest that niridazole might be converted to an active compound by yeast metabolism. The results of the experiments with niridazole in the non-nutrient medium were compared with those of AF-2 and SQ18, 506, two agents which have been shown to be genetically active in the present assay system.

Synopsis In our studies of structure-activity relationships, three nitroanilines and nine nitroaminophenols were tested for their ability to induce mutations in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98. The compounds m-nitroaniline, 4-nitro-2-aminophenol, and 3-nitro-6-aminophenol were active in two or more of these strains. The compounds o-nitroaniline, 2-nitro-3-aminophenol, 3-nitro-4-aminophenol, 4-nitro-3-aminophenol, 3-nitro-2-aminophenol, 2-nitro-6-aminophenol, 2-nitro-4-aminophenol and 2-nitro-5-aminophenol were inactive, both in the presence and in the absence of S9 mix. The compound p-nitroaniline was also inactive in all tests with the possible exception of that in strain TA98 in the presence of S9 mix, where it was either very weakly mutagenic or non-mutagenic. The mutagenic activity or inactivity of these compounds appears to be dependent on the positions of the amino, nitro, and hydroxy groups in their chemical structures. Etude en mutagénèse des nitroanilines et nitroaminophénols sur Salmonella typhimurium.

Saccharomyces cerevisiae strain XV185-14C for reversion studies was used to investigate the genetic activity of alpha-benzene hexachloride dibutyl phthalate and trichloroethylene. The results indicate that none of the three compounds was genetically active when yeast cells were treated in phosphate buffer (pH 7.0) in the absence of metabolic conversion. However, in the presence of the 9000 g supernatant of mice liver homogenate, NADP, glucose-6-phosphate, phosphate buffer (PH 7.4), MgCl2, KCl, the components which were used for the metabolic conversion, trichloroethylene porved to be a powerful mutagen. It increases the frequency of homoserine, histidine and lysine revertants over those of the control levels. Trichloroethylene appears to induce frameshift as well as base substitution mutations.

In order to explore structure-activity relationships, 4,4'-diaminoazobenzene and four structurally related azo dyes were tested for their ability to induce gene mutations in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538, and TA98. Only 4,4'-diaminoazobenzene and 4,4'-N(beta-hydroxyethylamino)azobenzene were found to be active in the two frameshift strains TA1538 and TA98. Further tests were performed in strain TA98, both in the presence and in the absence of Aroclor 1254-induced rat or hamster liver S9 preparations. The amount of S9 used per plate was 50, 100, 150 or 300 microliters, which corresponds to 10, 20, 30 or 60% of S9 in S9 mix. 4,4'-Diaminoazobenzene was found to be mutagenic, and its mutagenicity depended on the percentage of S9 in S9 mix and the type of S9 fraction used. 4,4'-N-(beta-Hydroxyethylamino)azobenzene was less mutagenic than 4,4'-diaminoazobenzene, indicating a reduction in mutagenicity associated with the beta-hydroxyalkyl substituents. The other three azo dyes [4'-methyl-4-N,N-di(beta-hydroxyethylamino) azobenzene; 4'-amino-6-methyl-4-N,N-di(beta-hydroxyethylamino)azobenzene; and 4'-N(beta-hydroxyethyl-amino)4-N,N-di(beta-hydroxyethylamino)azobe nzene] were inactive, both in the presence and in the absence of the metabolic activation system. The use of the preincubation test did not alter the observed positive or negative response of these compounds. The importance of this finding is that the non-mutagenicity or decreased mutagenicity of these four compounds is predictable on the basis of their chemical structures. These azo dyes, like the non-mutagenic members of series of monocyclic aromatic amines, contain large substituents on one or both of the amino groups of the parent compound, in this case 4,4'-diaminoazobenzene. From our earlier data and the experiments discussed in this paper, we conclude that the study of structure--activity relationships can provide useful information for the prediction and interpretation of mutagenic responses.

The hair-dye coupler 2,4-diaminophenoxyethanol was tested for mutagenicity in the histidine-requiring mutants of Salmonella typhimurium (TA1535, TA100, TA1537, TA1538 and TA98). The tests were carried out in the absence and presence of uninduced as well as an Aroclor-1254-induced rat-liver microsomal activation system. In the absence and presence of uninduced S9 this compound was not mutagenic in all strains used. Negative results were also obtained in the presence of an Aroclor-1254-induced rat-liver microsomal activation system. The mutagenic activity of this compound was also investigated in 2 systems of yeast, the gene conversion system with strain D4 and the reversion system with strain XV185-14C. In the absence and presence of metabolic activation, no mutagenic effect was observed.

The genetic activity of the antimicrobial food additives AF-2 and H-193 has been investigated in Saccharomyces cerevisiae. The strains chosen for the present studies were D5 for the induction of mitotic recombinational events and XV185-14C for the induction of reversion of the mutants lys1-1, his1-7 and homs3-7. When three concentrations (25, 50 and 100 mug/ml) of AF-2 were used in the reversion system of strain XV185-14C, there was an increase in the frequency of hom+ and his+ revertants as a function of incubation time, while the lysine mutant exhibited a very low frequency of induced reversion. When AF-2 and H-193 were compared at the same concentration and exposure time, AF-2 exhibited a higher genetic activity in both systems than H-193. However, H-193 was genetically more active in inducing revertants than AF-2, when the comparison was made at the same survival level. Cells of both haploid and diploid strains were found to be more sensitive to inactivation by AF-2 than by H-193 It should be pointed out that the solubility of H-193 was lower (about 4 mug/ml saturation) than the solubility of AF-2 (120 mug/ml saturation). The haploid strain was more sensitive to both compounds than the diploid strain.

Two samples of 4-amino-2-nitrophenol were tested for mutagenicity in Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98, and TA100. Significant mutagenic activity was detected with a sample of this compound obtained from Aldrich (technical grade (Aldrich), TGA) both in the presence and in the absence of a rat-liver S9 metabolic activation mixture. When toluene-insoluble contaminants of the TGA product were separated and tested for mutagenicity, they were found to be mutagenic in the same strains as the TGA sample. After removal of these major contaminants from the TGA product its mutagenicity was reduced; a nonmutagenic sample was obtained by further purification. The other sample of 4-amino-2-nitrophenol, which was synthesized and purified in our laboratory, was nonmutagenic. H.p.l.c. profiles of the unpurified TGA sample and the purified samples revealed a large number of contaminants in the TGA product. Likewise, t.l.c. revealed the presence of contaminants in the TGA product.

This review analyzes relationships between chemical structure and biological activity for several series of compounds. Its focus is on mutagenicity and carcinogenicity and the predictability of these properties on the basis of the chemical structure. Examples are selected from monocyclic aromatic amines, benzidine derivatives, aminoazobenzene derivatives, nitrofurans, aflatoxins, and sterigmatocystins. Results from mutagenicity tests in Salmonella typhimurium are summarized, and their correlation with carcinogenicity is discussed. The review is concluded with generalizations on the usefulness of studies on relationships between chemical structure and mutagenic activity.

5 different histidine-requiring strains of Salmonella typhimurium were used to test the mutagenic activity of 7 different fractions of Athabasca tar-sand. None of the 7 fractions (bitumen, maltenes, asphaltenes, saturated, monoaromatic, diaromatic and polyaromatic hydrocarbons), showed positive mutagenic response in any of the Salmonella typhimurium strains. We have tested a wide range of concentrations. The results obtained so far are consistent with the lack of mutagenic activity of all investigated fractions in the absence and in the presence of metabolic activation. Assuming that there might be an association between the absence of mutagenic activity and the complexity of the tar-sand fractions, we investigated the effect of the polyaromatic hydrocaron fraction on the mutagenicity of the carcinogenic agent 2-aminoanthracene. The data obtained indicate clearly that the polyaromatic hydrocarbon fraction suppresses the mutagenic activity of 2-aminoanthracene.

The mutagenic and recombinogenic activities of furylfuramide, an antimicrobial food additive, were tested in a two-component heterokaryon of Neurospora crassa and a diploid strain of Saccharomyces cerevisiae, respectively. The results show that furylfuramide is genetically active in both eukaryotic organisms; it induces mutations in Neurospora crassa and mitotic crossing over in Saccharomyces cerevisiae.

The hair-dye component N-methylamino-2-nitro-4-N', N'-bis(2-hydroxyethyl) aminobenzene was investigated for mutagenic activity in Salmonella typhimurium strains TA1535, TA100, TA1537, TA1538 and TA98. The testing was performed in the absence and in the presence of a rat-liver microsomal activation system induced by Aroclor 1254. Our results indicate that N-methylamino-2-nitro-4-N', N'-bis(2-hydroxyethyl)aminobenzene does not induce mutations in Salmonella typhimurium strains, either in the absence or in the presence of the metabolic activation system. The purity of the compound was controlled by utilizing high-pressure liquid chromatography (HPLC) and thin-layer chromatography (TLC).

We investigated the mutagenicity of m-diaminobenzene (m-phenylenediamine) and four 2,4-diaminoalkylbenzenes (methyl, ethyl, isopropyl and n-butyl) in Salmonella typhimurium strains TA100, TA1538 and TA98 in the absence and presence of S9 induced by Acoclor 1254. m-Diaminobenzene was the most active mutagen, followed by 2,4-diaminotoluene and 2,4-diaminoethylbenzene, resp. Negative response was observed for both 2,4-diaminoisopropylbenzene and 2,4-diamino-n-butylbenzene. Thus, depending on the size of the substituting alkyl group at the C1 position of 2,4-diaminoalkylbenzene, a decline and loss of mutagenic activity was observed.

The mutagenicity of fresh solutions of p-phenylenediamine (PPD) and Aroclor 1254 was investigated. The histidine-requiring strains of Salmonella typhimurium were used in the absence and presence of uninduced and/or Aroclor-induced rat-liver homogenate. The presence of polychlorinated biphenyls (PCBs) was also examined by chromatographic methods in Aroclor-induced rat-liver homogenate. In the absence of metabolic activation, as well as in the presence of uninduced rat-liver homogenate, PPD was not mutagenic in the strains used. In the presence of Aroclor-induced S9 a twofold increase (or less) was observed in the number of revertant colonies over those of the controls in TA1538 and TA98. There was no increase in the number of revertant colonies over those of the controls when PPD was dissolved in NH4OH solution and the solution mixed with H2O2 before the addition of S9 mix. Aroclor 1254 was not mutagenic in TA1538 or TA98. However, the presence of PCBs in Aroclor-induced rat-liver homogenate (induced S9) was identified by gas-liquid chromatography (GLC), high-performance liquid chromatography (HPLC) and gas--liquid chromatography/mass spectrometry (GC/MS).