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The Hangu Formation (Paleocene) consists of sandstone, siltstone, carbonaceous shale, coal and laterite. It is well exposed in the Trans Indus Surghar range and the southern Hazara basin. The sandstone is yellowish brown, fine to coarse grained and medium to thick bedded. The sandstone of the Hangu Formation is classified as quartz arenite on the Q-F-L diagram. It is mostly grain supported and are cemented by silica cement. The study of different stratigraphic sections reveal that Hangu Formation can be sub-divided into a number of lithofacies on the basis of sedimentary structures and lithological variations.These include lateritic lithofacies, coal and carbonaceous shale, cross-bedded sandstone, bioclastic limestone and bioturbated sandstone. All these lithofacies are well-developed in the Baroch Nala section of the Surghar range except the lateritic lithofacies which contains a thin bed of ferruginous clay. In the studied sections of the Hazara basin, the lateritic lithofacies is the only well-developed lithofacies present in the area. The coal occurs at two stratigraphic levels in the Baroch Nala section. The lower coal seam is thick and its chemical study indicates higher calorific value and carbon content than the upper coal seam and with low moisture/ash content. On the basis of the calorific value, the coal of the Hangu Formation is characterized as highvolatile bituminous. The degree of laterization is strong in the Langrial and Khanpur sections and moderate in Baroch Nala section

The function of the sperm storage tubules is directly correlated with the fertility of laying hens. However, little is known about the molecular mechanisms regulating the fertility traits in chicken. To identify genetic markers associated with reproductive traits, we calculated fertility rate at 61 to 69 wk (51 D) of Jing Hong chickens parent generation as the phenotype and the genotype were detected by the chicken 600K Affymetrix Axiom High Density single nucleotide polymorphisms (SNP)-array. The genome-wide association study using 190 Jing Hong hens showed that the 20 SNP in chromosomes 3 and 13 were significantly associated with fertility rate. To verify these results, a total of 1900 Jing Hong laying hens from 2 populations (P1 and P2) were further genotyped by polymerase chain reaction–restriction fragments length polymorphisms method. The association analysis results revealed that 12 polymorphisms (AX-75769978, AX-76582632, AX-75730546, AX-75730496, AX-75730588, AX-76530282, AX-76530329, AX-76529310, AX-75769906, AX-75755394, AX-80813697 and AX-76582809) out of 20 showed highly significant effects (P

Carbon (δ13C) and nitrogen (δ15N) isotopes were used to evaluate spatial, temporal, and interspecific differences in trophic relationships of four fish species (Paralichthys dentatus, Anchoa mitchilli, Leiostomus xanthurus, and Bairdiella chrysoura) in Maryland's coastal bays. The δ13C values for all species were more enriched in 2017 than in 2018, a year of higher-than-average rainfall that likely caused higher amounts of terrestrial carbon to enter the estuary. There were significant differences among species in the δ13C values, with L. xanthurus being the least depleted (−17.2‰ in 2017; −18.8‰ in 2018). Spatially, the δ13C values of the species, particularly P. dentatus and B. chrysoura, were more depleted in the northern bays, which have a higher nutrient content and receive more freshwater inflow directly from tributaries, than the southern bays. The observed δ13C values (−19.5 ± 0.2‰ to –17.2 ± 0.3‰), however, indicate that marine phytoplankton was the primary carbon source of the fishes. Overall, A. mitchilli was the most enriched in δ15N (13.0‰), and L. xanthurus was the most depleted (10.2‰). δ15N was more enriched in fish from the more human-impacted northern bays than in fish from the southern bays, though this might also have stemmed from the differences in the diet composition of the species in the northern and southern bays. A. mitchilli had the highest trophic level, while L. xanthurus and P. dentatus had the lowest trophic levels. Niche breadth was widest in L. xanthurus compared to the other fish species, suggesting a higher variability in diets among L. xanthurus individuals, leading to specialized diets. There was a high niche overlap between B. chrysoura, A. mitchilli, and L. xanthurus, which indicates they fed on similar prey resources. [ABSTRACT FROM AUTHOR]

Gurung, D.P.; Chen, N.; Waguespack, Y.; Ishaque, A.B., and Chigbu, P., 2024. Assessment of alkaline phosphatase activity in the water column of Maryland Coastal Bays. Journal of Coastal Research, 40(2), 319–337. Charlotte (North Carolina), ISSN 0749-0208. Understanding maximum alkaline phosphatase activity (Vmax) is essential to understand the phosphorus (P) cycle in Maryland Coastal Bays (MCBs). The objectives of this study were to measure Vmax in the samples collected from different locations in MCBs and to examine the relationship between Vmax and dissolved reactive phosphorus (DRP) concentrations. Water samples were collected at 13 sites from 2014 to 2016, and Vmax was measured in whole water by using 4-methylumbelliferyl phosphate as the fluorogenic substrate. Although the measured Vmax was affected by multiple factors, P limitation events were recognized from spatial/temporal distributions in Vmax values, which might not be reflected by DRP condition. Regression analysis did not yield a significant relationship between DRP and Vmax, and monthly averages of DRP and Vmax provide better evidence of the connection between DRP and Vmax, including P limitation (high Vmax) and alkaline phosphatase inhibition (low Vmax). Results from this study support the view that Vmax is a good indicator of availability of DRP in aquatic environments. More work is needed to further understand the relationship between Vmax and DRP, in particular, when strong P limitation occurs in the Bays. Moderate to strong positive relationships were observed between Vmax and chlorophyll a. Moderately negative relationships were observed between Vmax and salinity and between Vmax and pH, which may be attributed to freshwater inputs. Likewise, a moderate positive relationship was observed between Vmax and temperature for only some months. [ABSTRACT FROM AUTHOR]

Background: Osteopetrosis includes a variety of rare inherited skeletal disorders characterized by increased bone density and thickness. It has different clinical forms, including infantile autosomal recessive, intermediate autosomal recessive, and late-onset autosomal dominant forms. Intermediate autosomal recessive osteopetrosis (IARO) displays high variability. Case Report: A 10-year-old male presented to our pediatrics emergency department with abdominal distension, low-grade fever, and swelling of the rightmaxilla with associated discharge. His local physician had treated the lesion with drainage and aspiration of pus without improvement. Examination revealed pallor, hepatosplenomegaly, poor dentition, and dental caries. Eye examination showed reduced visual acuity, absent color vision, nystagmus, and bilateral optic nerve atrophy. Laboratory investigations showed anemia and thrombocytopenia. Radiography yielded classic features of osteopetrosis. Detailed intraoral examination revealed an area of exposed necrotic bone in the alveolar region of the rightmaxilla, leading to a diagnosis of IARO with underlying osteomyelitis. The intraoral wound was treated with bismuth iodoform paraffin paste dressing, and the infection was treated with antibiotics. Anemia and thrombocytopenia were managed supportively by transfusion of packed red blood cells and platelets. Conclusion: IARO commonly presents with multiple fractures, so the absence of fractures in our patient was unusual. Studies evaluating the intermediate variant are meager; hence, documenting its various presentations is essential to aid physicians in making early diagnoses. Osteomyelitis of the jaws is a feared complication in these patients. Therefore, practitioners need to be cautious of infections of dental origin. [ABSTRACT FROM AUTHOR]

ABSTRACT Pifithrin-α (PFT-α) is a reversible inhibitor of p53-mediated apoptosis, p53-dependent gene transcription, as well as down stream responsive gene function. In response to genotoxic agents, normal cells are instructed [...]

Bladder cancer is the ninth most frequently diagnosed cancer worldwide, and there is a need to develop new biomarkers for staging and prognosis of this disease. Here we report that cell lines derived from low-grade and high-grade bladder cancers exhibit major differences in expression of glycans in surface glycoproteins. We analyzed protein glycosylation in three low-grade bladder cancer cell lines RT4 (grade-1-2), 5637 (grade-2), and SW780 (grade-1), and three high-grade bladder cancer cell lines J82COT (grade-3), T24 (grade-3) and TCCSUP (grade-4), with primary bladder epithelial cells, A/T/N, serving as a normal bladder cell control. Using a variety of approaches including flow cytometry, immunofluorescence, glycomics and gene expression analysis, we observed that the low-grade bladder cancer cell lines RT4, 5637 and SW780 express high levels of the fucosylated Lewis-X antigen (Lex, CD15) (Galβ1–4(Fucα1–3)GlcNAcβ1-R), while normal bladder epithelial A/T/N cells lack Lex expression. T24 and TCCSUP cells also lack Lex, whereas J82COT cells express low levels of Lex. Glycomics analyses revealed other major differences in fucosylation and sialylation of N -glycans between these cell types. O -glycans are highly differentiated, as RT4 cells synthesize core 2-based O -glycans that are lacking in the T24 cells. These differences in glycan expression correlated with differences in RNA expression levels of their cognate glycosyltransferases, including α1–3/4-fucosyltransferase genes. These major differences in glycan structures and gene expression profiles between low- and high-grade bladder cancer cells suggest that glycans and glycosyltransferases are candidate biomarkers for grading bladder cancers. [ABSTRACT FROM AUTHOR]

The detail study of the Paleocene Hangu Formation consisting of sandstone, carbonaceous shale, coal, and laterite has been carried out for its source and reservoir rock potential in the Salt Range, Surghar Range, and Attock-Cherat Ranges. The TOC values of the shales range from 0.33-11.19 (2.97 wt. %) and are characterized as good to very good quality source rock except the samples from Attock-Cherat Ranges. Similarly, the free (S1) and cracked hydrocarbons (S2) amount are very small suggesting Hangu Formation as a poor source rock for free and cracked hydrocarbons except the samples from the Lumshiwal Nala. The generative potential, type of kerogen and thermal maturity calculated on the basis of TOC, S1, S2, HI, PI and Tmax all characterized Hangu Formation as fair to excellent gas or oil source, type III and mixed type III/II kerogen and immature source rock. The Hangu Formation sandstone is brownish to yellowish brown, fine to coarse grained, medium to thick bedded and massive in places. The major diagenetic changes observed in a sandstone of the Hangu Formation are; compaction, cementation, replacement and grain fracturing. The effect of mechanical compaction is more evident than that of chemical compaction. Grain contact ranges from pointed to long through sutured. The type of cement present includes silica-cement, calcite-cement, dolomite-cement, and iron-oxide cement. Silica-cement is present as both overgrowth and pore-filling cement. Clay rim is present around few grains. The process of early calcite cementation, mechanical compaction, silica, and iron oxide cementation destroys the reservoir properties of the Hangu Formation sandstone. There is no visible porosity observed except the dissolution of few grains at their margins. However, during the process of uplifting such porosity usually filled by the iron- oxide cementation. Hence, Hangu Formation is an immature source rock with a poor reservoir potential. [ABSTRACT FROM AUTHOR]

The suspended particulate organic matter (SPOM) in transitional waters such as the Maryland Coastal Bays (MCBs) is derived from allochthonous and autochthonous sources. Little is known, however, about the contribution of terrestrially derived organic matter to SPOM in the MCBs. The sources of SPOM in the MCBs were evaluated using stable isotope ratios of nitrogen (δ15N) and carbon (δ13C), and C/N molar ratios. The values of SPOM δ15N, δ13C and C/N ratios from samples collected seasonally (July 2014 to October 2017) at 13 sites ranged from −0.58 to 10.51‰, −26.85 to −20.33‰, and 1.67 to 11.36, respectively, indicating a mixture of terrestrial SPOM transported by tributaries, marine organic matter from phytoplankton, and sewage. SPOM δ13C levels less than −24‰, suggesting the dominance of terrestrially derived carbon, occurred mainly at sites close to the mouths of tributaries, and were less depleted at sites near the ocean. The mean value of SPOM δ13C was higher in October 2014 (−22.76‰) than in October 2015 (−24.65‰) and 2016 (−24.57‰) likely due to differences in river discharge. Much lower values (<4‰) of δ15N observed in February 2016 coincided with a high freshwater inflow that accompanied a major storm, indicating a strong influence of untreated sewage. Results from a two end-member mixing model suggest that on average, the SPOM in the MCBs is composed of 44% terrestrial materials with the highest percent contributions in October 2015 and 2016 (61%), and lowest (28%) in July 2015. The contribution of terrestrial materials to the SPOM was highest (58%) near the mouth of St. Martin River and lowest (25%) near the Ocean City inlet. SPOM composition and distribution in MCBs are, therefore, a function of land use, freshwater inflow, and water circulation that influence in situ phytoplankton production, and the transport and distribution of terrestrially derived materials. [ABSTRACT FROM AUTHOR]

The CAT-Tox (L) assay has recently been developed and validated for detecting and quantifying the specific molecular mechanisms that underlie toxicity of various xenobotic chemicals. We performed this assayto measure the transcriptional responses associated with 2,4,6-trinitrotoluene (TNT) and 2 of its byproducts [2,4 and 2,6-dinitotoluenes (DNTs)] to 13 different recombinant cell lines generated from human liver carcinoma cells (HepG2) by creating stabletransfectants of mammalian promoter chloramphenicol acetyltransferase (CAT) gene fusions. Cytoxicity test with the parental HepG2 cells, using the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazol ium bromide]-based assay for cell viability, yielded LC50 values of 10516 mug/mL for TNT in 1% dimethyl sulfoxide (DMSO), and >300 m;g/mL for DNTs, upon 48 h of exposure. TNT appeared to bemore toxic than 2,4-DNT, which also showed a higher toxicity compared to 2,6-DNT. Of the 13 recombinant constructs evaluated, 8 (CYP 1A1,GST Ya, XRE, HMTIIA, c-fos, HSP70, GADD153, and GADD45), 5 (c-fos, HSP70, GADD153, GADD45, and GRP78), and none showed inductions to significant levels (p<0.05), for TNT, 2,4-DNT, and 2,6-DNT, respectively.For most constructs, the induction of stress genes was concentration-dependent. These results show the potential for TNT and 2,4-DNT to cause protein damage and/or perturbations of protein biosynthesis (HSP70 and GRP78), alterations in DNA sequence or its helical structure (c-fos, GADD153, GADD45), and the potential involvement of TNT in the biotransformation process (CYP 1A1, GST Ya, XRE), and in the toxicokinetics of metal ions (HMTIIA). Within the range of concentrations tested (0-300 mg TNT or DNT/mL in 1% DMSO), no significant inductions (p>0.05) of NFKBRE, p53RE, CRE, and RARE were found. [ABSTRACT FROM AUTHOR]

Introduction A systematic review and meta-analysis of the available randomized controlled trials (RCTs) were conducted to investigate the efficacy and safety of dotinurad in hyperuricemic patients with or without gout. Dotinurad is a novel selective urate reabsorption inhibitor (SURI) that increases uric acid excretion by selectively inhibiting urate transporter 1 (URAT1). To the best of our knowledge, this is the first meta-analysis conducted to gauge the efficacy and safety of dotinurad.  Methods Electronic databases (PubMed, the Cochrane Library, and ClinicalTrials.gov) were searched from inception till March 2, 2021, according to the Preferred Reporting Items for Systematic Review and Meta-Analysis statement. Randomized controlled trials comparing the efficacy and safety of dotinurad with placebo- or active (febuxostat or benzbromarone) control were included. The eligible studies were analyzed with RevMan 5.3 Software (The Nordic Cochrane Centre, Cochrane Collaboration, Copenhagen). Results Four eligible studies, consisting of 684 hyperuricemic patients were included. The number of patients who achieved serum uric acid (sUA) levels ≤ 6.0 mg/dl favoured dotinurad 1 mg group as compared to placebo group (risk ratio {RR} = 39.27, 95% onfidence interval {CI}, 5.59 to 275.65; p = 0.0002), dotinurad 2 mg group compared with placebo group (RR = 45.36, 95% CI, 6.48 to 317.38; p= 0.0001), and dotinurad 4 mg group compared with placebo group (RR = 54.16, 95% CI, 7.76 to 377.77; p < 0.0001). Conversely, there was no significant difference in the number of patients who achieved the target sUA levels between dotinurad 2 mg and active control (RR = 1.00, 95% CI, 0.92 to 1.08; p = 0.91). Moreover, the percentage change in sUA levels from baseline to final visit favoured dotinurad 1 mg vs. placebo ((RR = 36.51, 95% CI, 33.00 to 40.02; p < 0.00001), dotinurad 2 mg vs. placebo (RR = 46.70, 95% CI, 42.53 to 50.87; p < 0.00001), and dotinurad 4 mg vs. placebo (RR = 63.84, 95% CI, 60.51 to 67.16; p < 0.00001), while no significant difference was seen in dotinurad 2 mg vs. active control (RR = -0.08, 95% CI, -4.27 to 4.11; p= 0.97). Compared with active or placebo control, dotinurad 2 mg showed no significant difference in the number of events of gouty arthritis (RR= 1.31, 95% CI, 0.47 to 3.71; p = 0.60), the number patients with adverse events (RR = 1.09, 95% CI, 0.91 to 1.30; p = 0.36), and the number of patients who experienced adverse drug reactions (RR = 1.00, 95% CI, 0.68 to 1.47; p = 0.99). Conclusion Dotinurad shows significant improvement in serum uric acid levels in hyperuricemic individuals with or without gout. Its urate-lowering effect is comparable to the commonly available anti-hyperuricemic agents. Moreover, it is effective at doses 1 mg, 2 mg, and 4 mg and well-tolerated at a dose of 2 mg., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2021, Iqbal et al.)

In response to genotoxic agents, normal tissue cells are instructed by p53 either to perform DNA repair or to undergo apoptosis. Studies showed that chemo and/or radiotherapy damage both normal and cancerous cells indiscriminately. To this end, severe side effects inflicted by p53 activation in normal tissues, would possibly be abrogated by p53 inhibition. Pifithrin-alpha (PFT-alpha) is a reversible inhibitor of p53-mediated apoptosis, p53-dependent gene transcription, as well as down stream responsive gene function. The objective of this study was (1) to evaluate PFT-alpha for differential cellular protection in response to arsenic trioxide and cadmium chloride exposure of normal and neoplastic cells, and (2) to evaluate the transcriptional activation of p53 and p53-responsive genes in rat liver cells and HepG2 carcinoma cell line. Cell survival was detected by fluorescein diacetate (FDA) and fluorospectroscopy. Mean LC50 and (SD) for HepG2 cells following exposure to arsenic were 13.7 (+/-1.0) microg/ml with PFT- alpha and 13.4 (+/- 0.5) microg/ml without PFT-alpha (p>0.05). For rat liver cells it was 670 (+/- 8.15) microg/ml with and 573.15 (+/-1.0) microg/ml without PFT-alphha (p<0.05). On exposure to cadmium Chloride, LC50's were 6.95 (+/-2.5) microg/ml for HepG2 cell line in presence of PFT-alpha and 7.35 (+/-1.9) microg/ml in its absence (p>0.5). The results revealed significant differences from controls only upon exposure of rat liver cells to arsenic trioxide in presence of PFT-alpha. PFT-alpha inhibited the transactivation of p53 in rat liver cells and resulted in repression of Bcl2, PCNA, MDM2, Cyclin G and P21 genes by arsenic trioxide. HepG2 cells exposed to arsenic trioxide and PFT-alpha showed expression of only the P53 and PCNA genes. We conclude that PFT-alpha exhibits cytoprotective effect, modifies the detrimental influences of known genotoxic agents in normal cells and has the potential for use as an adjuvant to cancer therapy.

Although most researches with non-essential metals (NEMs) have been done with single or individual metals, in reality, organisms are often exposed to multiple contaminants at the same time through the air, food and water. In this study, we tested the toxicity of four NEMs, As, Cd, Pb, and Hg, individually and as a composite mixture using the microtox bioassay. This assay uses the reduction of bioluminescence of the bacterium Vibrio fischeri as a measure of toxicity. The concentrations of each chemical in the mixture were based on multiples of their maximum contaminant levels (MCLs) set by the U.S. EPA. The highest concentration of exposure was 20 times the MCL, which translated into 200, 100, 40 and 300 ppb for As, Cd, Hg and Pb, respectively. The ratio for the mixture from these concentrations was 10:5:2:15 for As, Cd, Hg and Pb, respectively. Among the individual metals tested, the ranking of toxicity was Hg>Pb>Cd>As based on the EC50 values of 109, 455, 508 and 768 ppb for Hg, Pb, Cd and As, respectively. The EC50 for the composite mixture was 495% MCL which translated into nominal concentrations of 49, 25, 10 and 74 ppb for As, Cd, Hg, and Pb, respectively. Overall, the EC50 value of each NEM within the mixture was lower than the EC50 of the individual chemical; an evidence of synergism for the mixture. The individual toxic units (TU) were 0.06, 0.05, 0.09, and 0.16 for As, Cd Hg, and Pb, respectively and the summed toxic unit (TU) was 0.37 (less than 1). This study provides needed scientific data necessary for carrying out complete risk assessment of As, Cd, Hg, and Pb mixtures of some priority compounds.

DNTs are considered possibly carcinogenic to humans (Group 2B) because there is inadequate evidence in humans for carcinogenicity though there is sufficient evidence in experimental animals. In this study, MCF-7 (breast) and MRC-5 (lung) cells were exposed to a serial dilution of 2,4 and 2,6 DNTs (control, 1-500 ppm) in 96 well tissue culture plates. After various time intervals (24, 48, 72 and 96 hrs) the plates were washed, and 100microl fluorescein diacetate solution (10 microg/ml in PBS) was added column wise to each well, and incubated at 37 C for 30 - 60 min before reading the fluorescence with a spectrofluorometer at excitation and emission wavelengths of 485 and 538 nm respectively. Spectrofluorometeric readings were converted to percentages of cell survival. Regression analysis was conducted to determine the relationship between cell survival and exposed concentration. Linear equations derived from the regression analysis were used to calculate the LC50 values. Results indicated that 2,6 DNT was more toxic to breast cells; LC50 values were 445 and 292 ppm at 24 and 48 hours respectively compared to 2,4 DNT showing LC50 values of 570 and 407 ppm at 24 and 48 hours, respectively. No significant differences in toxicity existed between the two chemicals with regard to lung cells. Contrary to the above observation, 2,4 DNT was more toxic to breast cells; LC50 values were 407 and 238 ppm at 24 and 48 hours respectively compared to lung cells showing LC50 values of 527 and 402 ppm at 24 and 48 hours respectively. No significant difference existed for 2,6 DNT between the two cell lines. Lungs cells were more resistant to the two chemicals.

Vitellogenin (vtg) concentrations were measured in plasma and liver samples from 12 hybrid Tilapia oreochromis niloticus x O. aureus to compare concentrations in these tissues. The results were calculated under two different normalizations: volume per gram of sample used (similar to normalization usually published in the literature and typically used for ELISA) and volume per total protein (similar to normalization used in polyacrylamide gel electrophoresis; PAGE). It was observed that the normalization procedure used in PAGE (per gram total protein) minimized the method detection limit by about 1000 and 2500 times in plasma and liver respectively, compared to the normalization usually reported in the literature. It was also observed that normalizing per gram total protein makes it possible to eliminate a potential problem of accidental dilution of plasma samples during sample collection. Moreover, the normalization on a per gram of total protein makes it possible even to compare results from the two different methods namely PAGE and ELISA. It also allows comparison between different tissues. Using the normalization procedures as used in PAGE (per gram total protein) for liver and the normalization method as reported in literature for ELISA (per volume of sample used), it was observed that liver samples had higher vtg levels (mean: 62 microg vtg/g) compared to the corresponding plasma samples (mean: 0.24 microg vtg/ml). However, when both results were normalized per gram total protein all but one liver sample were lower (62 microg vtg/g) than the corresponding plasma concentrations (mean = 246 microg vtg/g).

Embryos of the Japanese medaka (Oryzias latipes) were exposed to serial concentrations of atrazine (0, 25, 50, and 100 ppm) and arsenic trioxide (0, 0.025, 0.05, 0.1 ppm) until hatching. Stasis of circulation, blood islands, titanic convulsions, tube heart and mortality were observed in atrazine-treated embryos. Each endpoint exhibited a concentration-response relationship. Only 4% of the embryos hatched in the 25 ppm, and none in the 50 and 100 ppm, probably due to cell death attributed to the embryos' inability to break from the chorion. With arsenic exposure, hatching was inversely correlated to chemical concentration: 86%, 75% and 54% for 0.025, 0.05 and 0.1 ppm, respectively. Hatching periods were also reduced from 7-13 days in controls to 7-11 days in arsenic-treated embryos. This observation was more pronounced with the 0.05 ppm concentration, showing a reduction of about 4 days. Despite this shortage in hatching time, there were no observable morphological abnormalities, as seen with atrazine. The ecological significance of these findings and implications for the development of sublethal toxicity tests using Japanese medaka embryos are important.

Dinitrotoluenes (DNTs) are nitroaromatic compounds appearing as pale yellow crystalline solids at room temperature. Dinitrotoluenes exist as a mixture of 2 to 6 isomers, with 2,4-DNT, and 2,6-DNT being the most significant. About 500 persons are estimated to be potentially exposed yearly to 2,4-DNT and 2,6-DNT during the production of munitions and explosives. The main route of human exposure at ammunition facilities is inhalation, but dermal contact and inadvertent ingestion can also be substantial. In factory workers, exposure to DNTs has been linked to many adverse health effects, including cyanosis, vertigo, headache, metallic taste, dyspnea, weakness and lassitude, loss of appetite, nausea, and vomiting. Other symptoms including pain or parasthesia in extremities, abdominal discomfort, tremors, paralysis, chest pain, and unconsciousness have also been reported. The primary targets of DNT toxicity are the hematopoietic system (pallor, cyanosis, anemia, and leukocytosis), the cardiovascular system (ischemic heart disease), the nervous system (muscular weakness, headache, dizziness, nausea, insomnia, and tingling pains in the extremities) and the reproductive system (reduction of sperm counts, alteration of sperm morphology, and aspermatogenesis). An association between DNT exposure and increased risk of hepatocellular carcinomas and subcutaneous tumors in rats, as well as renal tumors in mice, has been established. Epidemiologic studies of DNT toxicity have been limited to small groups of workers who had been occupationally exposed at various ammunitions production facilities. Clearly defining the health effects of DNTs with a high degree of confidence has therefore been difficult because of the multigenic nature of occupational exposure. In an attempt to update the toxicologic profile of the DNTs, we hereby provide a critical review of the environmental and toxicologic pathology of DNTs, with a special emphasis on their potential implications for public health.

In response to genotoxic agents, normal cells are instructed by p53 to either perform DNA repair or to commit suicide. Since chemo and/or radiotherapy damage both normal and cancerous cells, the use of PFT-alpha, a reversible inhibitor of down stream function of p53, was suggested as a temporary inhibitor of p53-induced cell damage. Our objective therefore, was (1) to assess the inherent response of HepG2 and rat liver cells to the effects of arsenic and cadmium and (2) to evaluate the role of PFT-alpha in the differential protection of rat liver and HepG2 cells. Following cellular growth to 90% confluency, exposure to cytotoxic agents in presence of PFT-alpha (10 ppm) or its absence was performed. Cell survival was detected fluorometrically using fluorescein diacetate (FDA) and an Ascent Fluoroskan. Toxicity index (LC50) was calculated from percent survival using regression analysis. Results showed an average of 46 fold inherent resistance of rat liver cells to arsenic in comparison to HepG2 cells (LC50 range of 573.15-670 vs. 13.4-13.7 ppm respectively). An average of 8 fold inherent resistance was also attributed to rat liver cells in response to cadmium (LC50 range of 57.72-58.1 vs. 6.99-7.35 ppm respectively). PFT-alpha did not show significant difference in protecting HepG2 cells against cadmium or arsenic. In contrast, there was significant difference in the protection of rat liver cells upon exposure to arsenic. We conclude that Pifithrin-alpha exhibits protection to normal cells, which can play an important role in cancer chemotherapy.