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Fire is an important aspect for the health and environmental risks of nanomaterials. Although nanoparticle applications yield enhanced flame retardancy in polymer nanomaterials – due to char layer formation, the labyrinth effect, and molecular mobility depression – free nanoparticles (dry, dispersible single particles or agglomerates) may enter the gaseous phase during combustion processes, presenting an inhalation hazard. Vast research programmes initiated to develop novel nanostructured flame retardants for polymeric materials have already shown some beneficial effects, such as decreased heat release rate, limitation of dripping, and improvement of self-extinguishability. However, the health and environmental risks associated with the use of nanoparticles as fillers or flame retardants should be taken into account, as oxidative stress, fibrosis, cardiovascular effects, cytotoxicity, and possibly carcinogenicity as outcomes of nanoparticle exposure have been reported.

Myotonic dystrophy (DM; OMIM 160900, also known as dystrophia myotonica, myotonia atrophica and Steinert disease) is an autosomal dominant myotonic myopathy associated with abnormalities of other organs, including eyes, heart, endocrine system, central and peripheral nervous systems, gastrointestinal organs, bone, and skin.1 The mutation underlying DM is an expansion of an unstable cytosine-thymine-guanine (CTG) trinucleotide repeat in the 3' untranslated region of the myotonic dystrophy protein kinase (DMPK) gene in chromosome 19q13.3.2-4 In 1994, Thornton et al.5 described an autosomal dominant disorder similar to DM without CTG repeat expansion at the DM locus. Ricker et al.6 named this disease "proximal myotonic myopathy" (PROMM; OMIM 600109) because of predominantly proximal muscle weakness without atrophy as opposed to the distal muscle involvement seen in DM. Subsequently, Meola et al.7 described a variant of PROMM with unusual myotonic and myopathic features, which they named "proximal myotonic myopathy syndrome," and Udd et al.8 described a PROMM-like family with dystrophic features, which they named "proximal myotonic dystrophy" (PDM). Researchers at the University of Minnesota9,10 found another multisystemic myotonic disorder that closely resembles DM with distal muscle weakness but no CTG repeat expansion. Because of the close phenotypic resemblance to DM, they called this disease "myotonic dystrophy type 2" (DM2; OMIM 602668). In 1998, Ranum et al.9 assigned the DM2 locus to chromosome 3q in a large kindred. Shortly after that, Ricker et al.11 found that the majority of German PROMM families show linkage to the DM2 locus. PDM was also mapped to this region (Krahe and Udd, personal communication, 1999). Whether PROMM, PDM, and DM2 represent different phenotypic expressions of a disease caused by the same mutation or if they are allelic disorders remains to be determined. It is also possible that these disorders are caused by mutations in different genes that are closely linked in the chromosome 3q region.12 Furthermore, the disease loci in some typical PROMM families11 and other families with multisystemic myotonic disorders have been excluded from both DM and DM2 loci. Because of the genetic and phenotypic heterogeneity in this group of disorders, it became necessary to establish a new nomenclature foreseeing the future discovery of new disease loci and phenotypic variability.

The present stage of our preclinical investigations of targeted radiotherapy for melanoma with 3,7-(dimethylamino)phenazathionium chloride [methylene blue (MTB)] labelled with astatine-211 (211At), an alpha-particle emitter, concerns toxicity of the treatment, as well as macro- and microscopic evaluation of its efficacy. Fragments of two human melanoma xenografts, pigmented HX118 and non-pigmented HX34 (used as a control), were implanted s.c. into nude mice subsequently treated with two doses of 211At-MTB injected i.v. Alterations in tumour growth rate were related to microscopic damage caused by 211At-MTB to the lesions, as determined by light microscopy using histopathological techniques. 211At-MTB-dependent growth inhibition of pigmented melanoma occurred either instantly or as a gradual reduction in the tumour growth rate. At a later stage, lesions that ceased to grow immediately consisted of quiescent, heavily pigmented tumour cells, as well as advanced fibrosis, and were extensively infiltrated by melanin-laden phagocytes. Large, unresorbed and often calcified necrotic deposits characterised the tumours responding gradually to the treatment. 211At-MTB remained non-toxic in normal organs. Only a relative number of small lymphocytes in the groin lymph nodes in a minority of animals was temporarily reduced, most often in conjunction with the treatment of pigmented tumours. The data demonstrated a high therapeutic effectiveness of 211At-MTB towards pigmented melanoma at the expense of negligible injury to normal tissues, and revealed that the macroscopic determination of tumour growth rate often underestimated an efficacy of the applied treatment.

Background: Changes in gastroduodenal blood flow have been implicated in the pathogenesis of duodenal ulcer. We have studied duodenal blood flow during the development of an acute to chronic duodenal ulcer by using the abscopal model, in which ulcers are generated as an indirect effect of lower mediastinal irradiation. Methods: Female CFLP mice (n = 108) weighing 25–40 g were randomly allocated to one of three groups. Controls were not irradiated. Irradiated ‘controls’ received 18 Gy 250 kV X-rays to the upper mediastinum (which does not cause duodenal ulceration). The lower mediastinum group received the same dose of irradiation, which has been shown to induce typical chronic duodenal ulcers in 45% of animals so treated. Animals were studied by means of radiolabelled microspheres 3 or 7 days later (that is, during and at the end of the lag period for ulcer induction). Results: Proximal duodenal blood flow specifically was reduced by 32% in the lower mediastinum group compared with irradiated controls at ...

The effect of drying temperature of the black currant juice on the retention of vitamin C and anthocyanins content as well as drying kinetics in the freeze-dried process, has been studied. Non clarified, black currant juice was freered on plates in the layer of 15 mm thick until the temperature of -30 °C in the thermal center of sample has been reached. Plates with frozen layers of juice were subject of freeze-drying process at 5 different temperatures of the heating plate (20, 30. 40, 50 and 60 °C). Studies of the retention of vitamin C and anthocyanins after, drying were carried out. freeze-drying of black currant juice should be carried out at the temperature not higher than 40°C to preserve content of vitamin C and anthocyanins.

Mice were exposed to a single dose of 9 or 15 Gy of X rays directed to the stomach. Histamine and histamine formation capacity (HFC) in the oxyntic region of the stomach were assayed at regular intervals for 7 weeks. After 9 Gy, mean gastric mural histamine fell to 61% of the control value (p less than 0.01) 7 days after irradiation while HFC rose to 172% (p less than 0.05). Both histamine and HFC returned to control values within 2 weeks after irradiation. With 15 Gy, on Day 7, histamine fell to 46% (p less than 0.01) and HFC rose to 260% (p less than 0.05). Histamine concentration remained low (less than half of the control value) while HFC returned to normal. These dose-dependent changes in histamine were observed neither elsewhere in the gut nor in the circulating blood. Further groups of mice were exposed to 3, 6, 9 or 15 Gy to the stomach, with gastric histamine and HFC assayed on Day 7. Histamine concentration was inversely related to dose (r = -0.59, p less than 0.001) and HFC was directly dose dependent (r = 0.52, p less than 0.001). These results suggest that irradiation of the stomach may reduce gastric histamine without inducing a general histamine release. The depletion of the gastric histamine store may explain the inhibitory effect of irradiation of the stomach on gastric acid secretion.

The first part of the review outlines the classical interpretation of radiation damage to normal organs based on dose-response relationships for clonogenic cell survival and tissue kinetics. Proliferative organization of critical cell lineages (three-compartmental or H-type and one-compartmental or F-type) is considered as an additional determinant in the development of overt radiation injury. This leads to testable predictions concerned with divergent outcomes of stimulation of cell proliferation after radiation exposure using polypeptide growth factors. The prediction of favourable effects of such stimulation in H-type lineages is borne out by recent experiments on treatment with cytokines of radiation-induced haemopoietic insufficiency. The second prediction of deleterious effects of proliferative stimulation in recently, heavily irradiated F-type cell lineages remains to be verified or refuted.

Groups of mature Large White female pigs, approximately 10 months of age, received single intravenous infusions of 1.5, 2 or 2.5 mg/kg body weight (equivalent to approximately 90, approximately 120 and approximately 150 mg/m2) cisplatin. Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured before and at 4 weeks after cisplatin infusion by renography using [99 mTc]-DTPA (diethylenetriamminepentaacetic acid and iodohippurate sodium I 131, respectively. The left kidney of each cisplatin-treated animal plus that of four age-matched control pigs was then removed surgically, and GFR and ERPF were measured in the remaining kidney at 4 weekly intervals for up to 24 weeks after unilateral nephrectomy (UN). The pigs treated with cisplatin exhibited no consistent change in either GFR or ERPF at 4 weeks after treatment. A histological evaluation of kidneys from animals treated with greater than or equal to 2 mg/kg cisplatin that had been removed at UN revealed both tubular and glomerular lesions. The latter consisted of cell proliferation on the parietal surface of the urinary space; damage to the S1 portion of the proximal convolution was also noted. Following UN there was a pronounced dose-dependent reduction in the functional status of the remaining kidney such that the increase in GFR and ERPF in pigs initially receiving 2.5 mg/kg cisplatin was less than 50% of that seen in age-matched UN controls. Moreover, the glomerular lesions observed at 4 weeks after cisplatin infusion had apparently progressed to glomerular hyalinisation by 24 weeks after UN. Thus, prior treatment with cisplatin may cause a permanent reduction in renal functional reserve that may be clinically "silent" until exposure to an additional nephrotoxic insult.

Oral treatment with the H2-antagonist ICI 162,846 or omeprazole for five days inhibited both basal and pentagastrin stimulated acid secretion by 50% or more in mice. Either treatment increased the luminal secretion of histamine in the basal (12-fold) and stimulated (9-fold) states. Mice treated with the H2-antagonist had a 27% reduction (p less than 0.05) in mural histamine in the acid-producing area of the stomach. Mice were treated so as to induce duodenal ulcers (abscopal model) and were then treated with the H2-antagonist ICI 162,846, omeprazole or vehicle, orally for one week. Fewer duodenal ulcers were found in animals receiving drug treatments than in the oral vehicle group. Both the H2-receptor antagonist and the proton pump blocker inhibit acid production; acid blockade by either drug is accompanied by a massive increase in secretion of histamine. This rise was associated with depletion of the gastric histamine store only with H2-receptor blocker. Both means of acid inhibition reduce the formation of ulcers in this model.

This article focused on a number of aspects of the preparation of chromatin and other DNA-protein complexes for conventional transmission EM that are critical for success but may not have been addressed in a single chapter before. These include the importance of optimizing fixation, the generation of active supporting supports, and the use of negative staining as a means of obtaining higher resolution detail than can be garnered from shadow casting methods.

Vagotomy and omeprazole effectively inhibited 2-deoxy-D-glucose (-91%) and pentagastrin (-72%) stimulated acid production in mice, respectively. Both vagotomy and omeprazole treatment were accompanied by massive increases in histamine secretion (8-fold or more, during both basal and stimulated states). Mucosal stores of histamine, however, were not depleted. Similar rises in luminal histamine have been observed in patients treated in these ways. The mouse model may thus be suitable to elucidate the kinetics of histamine release in patients.

Targeted radiotherapy with 211At-methylene blue (211At-MTB) is a systemic treatment selectively directed at melanoma due to a high affinity of MTB to melanin synthesized in the tumor cells. Since MTB forms a strong complex with melanin, it is an effective carrier for a number of radioisotopes to be addressed to the tumor deposits of any size including individually dispersed melanoma cells. Thus, appropriately radiolabeled MTB can be used for either diagnosis or therapy of the neoplasm. As predicted and found in animal experiments, 211At-MTB is most effective therapeutically. Histopathological investigations showed that the highly pigmented 211At-MTB-treated tumors were characterized initially by perivascular oedema and hydropic degeneration of tumor cells followed by gradual development of extensive areas of coagulative necrosis. The necrotic tumor areas contained microvessels occluded by thrombi and tended to undergo microfocal calcification. Although melanoma-bearing animals successfully treated with 211At-MTB did not reveal any adverse effects of the therapy, detailed toxicological studies were undertaken. No serious macro- or microscopic lesions were observed in normal organs of 211At-MTB treated mice. Only the relative number of small lymphocytes in the groin lymph nodes in a minority of animals was variably reduced, most often in conjunction with the treatment of highly, but not poorly, pigmented tumors.

In addition to transiently inhibiting cell cycle progression and sterilizing those cells capable of proliferation, irradiation disturbs the homeostasis effected by endogenous mediators of intercellular communication (humoral component of tissue response to radiation). Changes in the mediator levels may modulate radiation effects either by assisting a return to normality (e.g., through a rise in H-type cell lineage-specific growth factors) or by aggravating the damage. The latter mode is illustrated with reports on changes in eicosanoid levels after irradiation and on results of empirical treatment of radiation injuries with anti-inflammatory drugs. Prodromal, acute and chronic effects of radiation are accompanied by excessive production of eicosanoids (prostaglandins, prostacyclin, thromboxanes and leukotrienes). These endogenous mediators of inflammatory reactions may be responsible for the vasodilatation, vasoconstriction, increased microvascular permeability, thrombosis and chemotaxis observed after radiation exposure. Glucocorticoids inhibit eicosanoid synthesis primarily by interfering with phospholipase A2 whilst non-steroidal anti-inflammatory drugs prevent prostaglandin/thromboxane synthesis by inhibiting cyclooxygenase. When administered after irradiation on empirical grounds, drugs belonging to both groups tend to attenuate a range of prodromal, acute and chronic effects of radiation in man and animals. Taken together, these two sets of observations are highly suggestive of a contribution of humoral factors to the adverse responses of normal tissues and organs to radiation. A full account of radiation damage should therefore consist of complementary descriptions of cellular and humoral events. Further studies on anti-inflammatory drug treatment of radiation damage to normal organs are justified and desirable.

There is a new model of chronic duodenal ulcer in which the ulcer is generated by irradiating the lower mediastinum of mice with a single dose of 18 Gy 250 kV x rays. Single ulcers develop in the proximal duodenum of about half the animals. Previous studies have shown a remarkable morphological and behavioural similarity to duodenal ulcer in man. Ulceration occurs because of an imbalance between aggressive and defensive forces within the duodenum and an attempt has been made to elucidate the pathomechanism of this ulcer by determining acid and pepsin secretion. The basal and pentagastrin stimulated secretion of acid, pepsin, and histamine were measured and no changes in acid or pepsin secretion were shown to occur (risk of type II error < 1%). It is therefore concluded that this chronic ulcer is a model of impaired duodenal defence.

A mathematical model has been used to investigate the relationship of curability to tumour size and cell number for spherical tumours treated with targeted 131I or 90Y, assuming uniform uptake of radionuclide throughout the tumour. The analysis shows that, for any given cumulated activity per unit mass of tumour, cure probability is greatest for tumours whose diameter is close to an optimum value which depends on the path length of the emitted beta-particle. Smaller tumours are less curable because of inefficient absorption of radiation energy, and larger tumours are less curable because of greater clonogenic cell number. The lesser curability of very small tumours is a feature of targeted radiotherapy using long-range beta-emitters which does not occur with external beam irradiation. The predicted inefficiency of sterilisation of microscopic tumours poses a problem for targeted radiotherapy which is analogous to "geographic miss" in conventional radiotherapy. The implication is that small micro-metastases could escape sterilisation by radionuclides administered at activity levels sufficient to eradicate larger tumours. It is suggested that single agent targeted radiotherapy should not be used for treatment of disseminated malignancy when multiple tumours of differing size, including micrometastases, may be present. The analysis implies that an advantage might result from the use of a panel of several radionuclides (including short-range emitters) or from combining targeted radiotherapy using long-range beta-emitters with external beam irradiation or some other modality to which microscopic tumours are preferentially vulnerable.

Purpose: The use of an EPID in the clinic typically requires manual translations of the device based on light fields. These manipulations potentially are time‐consuming and prone to errors; accidental irradiations of the electronics components of EPIDs can shorten their lifetime and degrade the image quality. To eliminate these laborious manipulations in the treatment room, we have developed a custom application dedicated to the verification and correction of the portal imager position. Method and Materials: The application has been developed in Matlab and was compiled as a standalone application. Two versions were developed to accommodate the particularities of the two EPIDs available at our institution (aS500 (Varian) and iViewGT (Elekta)). Based on the treatment plans of the requested patient, the software loads the parameters required to simulate treatment fields. The graphical user interface shows the selected fields with the detector limits, so that the user can modify the fields requiring double exposition or cropping for imaging. Afterward, the user verifies the portal imager positioning and manually or automatically finds, if necessary, the proper imager translation. Results: At our institution, this application allows technologists to prepare EPID positioning while they are doing the final plan verification of a patient. Since the introduction of this application, the treatment time of plans having large or asymmetrical fields was reduced of at least one minute (of a 15 to 30 min time slots every day) and the risk of irradiating EPID's electronics was decreased or eliminated. Conclusion: This application streamlines the clinic workflow and saves time in the treatment room. In addition, because it has the potential to reduce accidental EPID's electronics irradiations, it can help to preserve their image quality in the long term.

Purpose: To present results obtained during the acceptance of the Gemini GXL PET/CT Simulator system. Method and Materials: A flat radiotherapy tabletop is permanently installed on our system. CT Simulator acceptance was performed using the TG‐66 Tables II and III as templates. Two 60‐cm long CT Sim phantoms were used. The relative electron density (RED) to HU relationship was measured with the RMI 465 and Catphan 600 phantoms and analysed using the stoichiometric method of Schneider et al. HU uniformity was measured with a 20‐cm water phantom and contrast‐to‐noise (CNR) performance measured with the Catphan. PET performance was measured using the NEMA 2‐2001 standard at the factory before shipment and after installation. Results: Table sag was measured to be +/− 4 mm over a 1200 mm scan range with loads of 0 to 282 lbs. During longitudinal table displacements, a 2–3 mm shift occurs over a 300 mm range and makes it impractical to use the head‐end of the table in some applications. The slice sensitivity profiles for the 0.75 and 1.5 mm nominal slice thickness were measured to be 1.1 and 1.8 mm. From the RMI 465 and Catphan measurements, a RED‐HU relationship applicable to biological tissues at 120 and 140 kVp was developed. HU uniformity for water was measured to be +10 HU to −12 HU for clinical protocols. Image quality is evaluated by quantifying the CNR for a 15 mm object. PET peak true count rate and peak NEC rate performance measured at the factory and at installation are below manufacturer published specifications: (191, 182 vs 203 kcps) and (61, 56 vs 70 kcps). Conclusion: Future work will involve evaluating PETspatial resolution at 20 cm off‐axis positions, quantifying the impact of table load on PET/CT fusion accuracy and developing tools to permit clinical PET/CT simulation.

The total cross section for hadron production by high-energy photons has been measured from a number of nuclei ranging from hydrogen to uranium. Some shadowing is observed at a level considerably less than predicted by conventional vector-meson dominance but consistent with a modified theory. The energy dependence predicted by vectormeson dominance is observed. The shadowing in heavy nuclei shows a smooth transition from electroproduction to photoproduction.

A single dose of 9 or 15 Gy of X-rays was given to the stomach of mice. Gastric histamine formation capacity (HFC) rose in a dose-related fashion during days 4 to 11 after irradiation. This rise coincided with a dose-dependent fall in gastric mural histamine concentration. 15 Gy X-rays also resulted in a transient loss of body weight (days 4-8 after irradiation). These results suggest that irradiation of the stomach mobilizes gastric histamine and that gastric histamine stores may be radiosensitive.

Total cross sections for electron-positron pair production by photons have been measured in the energy range 1--10 GeV from nuclei ranging from hydrogen to uranium. The results agree, with a precision of about 2% over the full range, with calculations of Tsai.

The response of normal tissues is vital in assessing any cancer treatment. Reasons are discussed why the response of normal structures in small animals is thought to be relevant to that in man. Endpoints for damage to a variety of normal tissues are considered and examples of dose response curves for many of these systems, taken from the published literature, are used as illustrations.

It is argued that proliferating normal tissues fall into two categories. In type H (for hierarchical) tissues, cells either multiply or perform tissue-specific functions. Sterilizing doses or radiation immediately initiate a gradual depopulation of irreversibly postmitotic, mature cells. The constant rate of functional cell depletion is given by physiological longevity of the cells. Consequently the onset of maximal depopulation is dose-independent and, after a range of radiation doses, the peak of milder damage is seen earlier than that of a more severe one. In type F (for flexible) tissues all cells are assumed to have the potential for proliferation and are also engaged in tissue-specific functions. Radiation leads to dose-dependent loss of the functional cells through their mitotic death, both immediately after exposure and during the next phase of increased compensatory proliferation resulting in accelerated expression of radiation damage ('avalanche'). Consequently the more severe damage following larger doses of radiation is seen earlier than the milder one produced with smaller doses. Assays of cell clonogenicity in vivo concern almost exclusively type H populations. The large radiation/drug/heat doses administered in these assays serve both to dilute the clonogenic cells by at least two orders of magnitude, and to produce a measurable response. When comparing two agents or interpreting their combined action it is advisable to ensure that the dilution step yields qualitatively comparable samples of clonogenic cells to be then characterized in terms of dose-survival curve parameters.

Biological properties of a spontaneous murine tumour (STS) suitable for in vitro - in vivo studies

A new type of optical spark chamber, capable of supporting many tracks, is described. The essential new feature is a thin conductive layer over a thin insulation layer which is attached to one of the plates of a conventional chamber. Theory of operation and experimental tests are described.

The total cross-section for production of hadrons by inelastic electron scattering at 3.2° from hydrogen and deuterium has been measured in the Q 2 range 0.015 GeV 2 to 0.1 GeV 2 , at virtual photon energies ranging from 2 GeV to 8.5 GeV. The transition to photoproduction is observed to be smooth, the ratio σ D /σ H being about 1.85 in this range. No evidence is seen for a conjectured rapid Q 2 -dependence of this ratio at low Q 2 .

In a new model, chronic duodenal ulcers are generated by irradiating the lower mediastinum of mice with single doses of X-rays. Histamine, a potent secretagogue, may have a role in the aetiology. Seven days after irradiation, the lag period for ulcerogenesis, mice were given a gastric perfusion test. In mice given irradiation to the lower mediastinum tissue histamine in the oxyntic region of the stomach assayed after perfusion was significantly lower than that of controls. Acid and peptic activity were not different from controls. Histamine release may mediate the abscopal ulcer without increasing acid and peptic activity.

The total cross section for hadron production by inelastic electron scattering at 3.2$pi$ from a number of nuclei has been measured at several virtual photon energies at fixed Q$sup 2$=0.1 (GeV/c)$sup 2$. The hadronic cross section is measured directly, by detecting at least one hadron in coincidence with the scattered electron. The results show very little shadowing and no detectable energy dependence. These observations contradict vector-meson dominance. (AIP)

Polymerization of isoprene over Al2O3 doped with potassium and sodium vapors has been investigated. The product is polyisoprene with a high content of 3,4-structures.

The neutron therapy facility based on the cyclotron installed in the Institute of Nuclear Physics in Krakow, Poland, is described. Fast neutrons are produced by bombarding a beryllium target with 12.5 MeV deuterons. The unit has been used for treatment of cancer patients by the medical team of the Institute of Oncology in Krakow since September, 1978. Fifty-three patients were treated; most of these patients had advanced head and neck cancer. On the basis of the radiobiological experiments, a standard tumor dose of 1320 radn,gamma in 20 fractions over 4 weeks was established. From among 34 patients with advanced head and neck cancer, treated with neutrons only, and observed for at least one year, 10 patients, (29%) are living free of cancer.

The primary effect of irradiation on self-renewing normal tissues is sterilisation of their proliferative cells, but how this translates into failure of tissue function depends on the mode of organisation of the tissue concerned. It has recently been suggested (Michalowski, 1981) that proliferative normal tissues may be classed as "hierarchical" (like haemopoietic tissues) or as "flexible" (like liver parenchyma) and that radiation injury to tissue function develops by different pathways in these tissues. Mathematical model studies confirm the different radiation responses of differently organized tissues. Tissues of the "flexible" or "F-type" category display a variety of novel radiobiological properties, different from those of the more familiar "hierarchical" or "H-type" tissues. The "F-type" responses are strongly influenced by radiation-sterilised ("doomed") cells, and it is suggested that the role of "doomed" cells has been undervalued relative to that of clonogenic survivors. Since "F-type" tissues have characteristically low rates of cell renewal, it is possible that these tissues are preferentially responsible for late effects of irradiation in clinical radiotherapy.

During the past several years a number of projects have studied the feasibility of using robots to serve the needs of the severely disabled (1–4). The goal has been to build a device for use in the performance of activities of everyday living, as well as in recreational and vocational tasks, by persons whose upper and lower limb functions are impaired due to disease or injury.

Gastric irradiation selectively inhibits acid secretion. Histamine may have a role in the inhibitory process. Seven days after gastric irradiation with 9 Gy X-rays, mice underwent a stomach perfusion and secretion test. Under pentagastrin stimulation (62.5 micrograms/kg), acid and histamine secretion was significantly lower than that of the unirradiated controls, while pepsin and potassium outputs were unchanged. Histamine concentration in the oxyntic region of the stomach assayed after the perfusion test was significantly lower than that of controls. It is postulated that the fall in the endogenous histamine store may contribute to the reduction in acid production.

We welcome the comments by Fowler (1983) on our recent paper (Wheldon et al, 1982), and in particular his agreement on the need to distinguish clearly between the dose-response curves for gross injury and/or impairment of tissue function and those for reproductive survival of clonogenic cells. Fowler points out that “There must be some relationship between them but it is not necessarily independent of radiation dose”. In our recent model of the radiation responses of slowly proliferating normal tissues (“Type F” tissues, Wheldon et al, 1982) this relationship is indeed shown to be dose-dependent and leads to a systematic difference in shape between the two dose-response curves.

Assessment of radiation damage to normal tissues in terms of dose-response curves for infinite proliferative potential ("survival curves") does not take into account the decrease with increasing dose of the multiplication rate of the clonogenic and non-clonogenic (radiation-sterilized) cells which may be implicated in the expression of the damage to tissue function or gross appearance. While radiation selectively lowers the chance of successful mitotic divisions, other anticancer agents may in addition interfere with different cellular processes. Comparisons of effectiveness of radiation with that of other modalities should not therefore be limited to analysis of survival curves. Assays of cell "survival" in self-renewing normal tissues in situ often define properties of a non-random sample of the clonogens. The nature of repair associated with the post-irradiation delay in performance of transplantation assays for normal clonogenic cells remains unclear. Dose-response relationships for functional impairment or gross damage to tissue, especially those obtained by irradiation with many fractions, do not necessarily yield to interpretation in terms of clonogenic cell "survival".