Synthesis of new kojic acid based unnatural α-amino acid derivatives.

An efficient method for the preparation of kojic acid based α-amino acid derivatives by alkylation of glycinate schiff base with bromokojic acids have been described. Using this method, mono as well as di alkylated kojic acid-amino acid conjugates have been prepared. This is the first synthesis of C-linked kojic acid-amino acid conjugate where kojic acid is directly linked to amino acid through a C-C bond.

Mushroom beta glucan: potential candidate for post irradiation protection.

The in vivo radioprotective effect of a beta-glucan (BG) isolated from the mushroom Ganoderma lucidum, against radiation (RT) induced damage was investigated taking mouse survival, hematology, liver GSH (Reduced glutathione), liver Malondialdehyde (MDA) and bone marrow chromosomal aberrations as end points. Young adult swiss albino mice were whole body exposed to gamma radiation. For mouse survival study, BG was administered orally (250µg/kg body wt or 500µg/kg body wt) 15min before or 5min after 8Gy exposure. For other parameters BG was given orally 5min after 4Gy exposure. The radioprotective effect of BG was compared with that of clinically used radioprotective drug amifostine (WR-2721), at 300mg/kg body wt administered intraperitoneally, 30min before irradiation. BG (500µg/kg body wt) produced (66%) mouse survival at 30 days given post irradiation, and 83% survived at 30 days with 300mg/kg body wt of amifostine administered before RT while RT alone produced 100% mortality. BG is not toxic at the radioprotective dose. Significant reduction in number of aberrant cells and different types of aberration was observed in both BG and amifostine administered groups compared to radiation alone treated group. BG seems to have potential for use in protection against unplanned radiation exposures.

Radioprotective effect of sulfasalazine on mouse bone marrow chromosomes.

Sulfasalazine (SAZ), a prescribed drug for inflammatory bowel disease, is a potent scavenger of reactive oxygen species. The present study was undertaken to ascertain its ability to protect against gamma radiation-induced damage. Acute toxicity of the drug was studied taking 24-h, 72-h and 30-day mortality after a single intraperitoneal injection of 400-1200 mg/kg body weight (b.wt.) of the drug. The drug LD(50) for 24- and 72-h/30-day survival were found to be 933 and 676 mg/kg b.wt., respectively. The optimum time of drug administration and drug dose-dependent effect on in vivo radiation protection of bone marrow chromosomes was studied in mice. Injection of 30-180 mg/kg SAZ 30 min before gamma irradiation (RT) with 4 Gy produced a significant dose-dependent reduction in the RT-induced percent aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h after exposure, with a corresponding decrease in the different types of aberrations. The optimum dose for protection without drug toxicity was 120 mg/kg b.wt. At this dose, SAZ produced >60% reduction in the RT-induced percent aberrant metaphases and micronucleated erythrocytes. SAZ also produced a significant increase in the ratio of polychromatic erythrocytes to normochromatic erythrocytes from that of irradiated control. Injection of 120 mg/kg of the drug 60 or 30 min before or within 15 min after 4 Gy whole-body RT resulted in a significant decrease in the percent of aberrant metaphases and in the frequency of micronucleated erythrocytes at 24 h post-irradiation; the maximum effect was seen when the drug was administered 30 min before irradiation. These results show that SAZ protect mice against RT-induced chromosomal damage and cell cycle progression delay. SAZ also protected plasmid DNA (pGEM-7Zf) against Fenton's reactant-induced breaks, suggesting free radical scavenging as one of the possible mechanism for radiation protection.

Enhancement of radiation induced cell death in chicken B lymphocytes by withaferin A.

Withaferin A (WA), a plant withanolide, has shown significant radiosensitizing effect in vitro and in vivo. Inhibition of DNA repair has been suggested as a mechanism of radiosensitization by WA. To test this, the effect of withaferin A on survival of DT40 chicken B-lymphocyte cell line and its repair deficient single gene mutants Rad54-/-, Ku70-/- and double mutant Ku70-/- /Rad54-/- after irradiation was studied. Exponentially growing cells were treated for 1 hr with 5 microM WA and then exposed to different doses of X-rays. Cell survival was studied by clonogenic assay. WA significantly reduced survival of DT40, Ku70-/- and Ku70-/- /Rad54-/-, but not Rad54-/- cells, suggesting that WA enhances radiosensitivity by interfering with homologous repair, the major pathway of DSB repair in these cells. Inhibition of DNA repair is further indicated in a significant decrease in surviving fraction of DT40 cells by post-irradiation incubation with WA. This could have relevance to cancer radiotherapy.

Modulation of pentylenetetrazole-induced seizures and oxidative stress parameters by sodium valproate in the absence and presence of N-acetylcysteine.

In view of a role of oxidative stress in epilepsy and the evidence for the involvement of peroxidative injury in sodium valproate (SVP)-induced adverse effects on liver and kidneys, we investigated whether the combination of SVP with N-acetylcysteine (NAC), an antioxidant, may help us to achieve maximal efficacy in terms of seizure control, with minimal toxicity on liver and kidneys. Pentylenetetrazole (PTZ)-induced seizures were used to evaluate the anticonvulsant effect of drugs. Biochemical estimations included the determination of oxidative stress markers like thiobarbituric acid-reactive substances in brain tissue and glutathione (GSH) levels in liver and kidney tissues. Aspartate aminotransferase and alanine aminotransferase concentrations in the serum were also determined to assess liver function. In our study, NAC exhibited a nondose-dependent anticonvulsant effect. The concurrent administration of NAC with SVP significantly prolonged the latency to jerks, myoclonus and clonic generalized seizures. No significant oxidative stress was evident in brain tissue following PTZ-induced seizures, though an elevation of serum transaminase enzymes was seen. SVP at the dose studied did not produce any significant oxidative stress on the liver and kidneys, while treatment with NAC elevated liver and kidney GSH levels. The concurrent administration of NAC with SVP had beneficial effects on liver and kidney cells.

Antipsychotic-like profile of thioperamide, a selective H3-receptor antagonist in mice.

Experimental and clinical evidence points to a role of central histaminergic system in the pathogenesis of schizophrenia. The present study was designed to study the effect of histamine H(3)-receptor ligands on neuroleptic-induced catalepsy, apomorphine-induced climbing behavior and amphetamine-induced locomotor activities in mice. Catalepsy was induced by haloperidol (2 mg/kg p.o.), while apomorphine (1.5 mg/kg s.c.) and amphetamine (2 mg/kg s.c.) were used for studying climbing behavior and locomotor activities, respectively. (R)-alpha-methylhistamine (RAMH) (5 microg i.c.v.) and thioperamide (THP) (15 mg/kg i.p.), per se did not cause catalepsy. Administration of THP (3.75, 7.5 and 15 mg/kg i.p.) 1 h prior to haloperidol resulted in a dose-dependent increase in the catalepsy times (P < 0.05). However, pretreatment with RAMH significantly reversed such an effect of THP (15 mg/kg i.p.). RAMH per se showed significant reduction in locomotor time, distance traveled and average speed but THP (15 mg/kg i.p.) per se had no effect on these parameters. On amphetamine-induced hyperactivity, THP (3.75 and 7.5 mg/kg i.p.) reduced locomotor time, distance traveled and average speed (P < 0.05). Pretreatment with RAMH (5 microg i.c.v.) could partially reverse such effects of THP (3.75 mg/kg i.p.). Climbing behavior induced by apomorphine was reduced in animals treated with THP. Such an effect was, however, reversed in presence of RAMH. THP exhibited an antipsychotic-like profile by potentiating haloperidol-induced catalepsy, reducing amphetamine-induced hyperactivity and reducing apomorphine-induced climbing in mice. Such effects of THP were reversed by RAMH indicating the involvement of histamine H(3)-receptors. Findings suggest a potential for H(3)-receptor antagonists in improving the refractory cases of schizophrenia.

Centella asiatica treatment during postnatal period enhances learning and memory in mice.

Present investigation was planned to evaluate the nootropic effect of Centella asiatica. Three months old male Swiss albino mice were injected orally with graded doses (200, 500, 700, 1000 mg/kg body weight) of C. asiatica aqueous extract for 15 days to select an effective dose for nootropic studies. Animals were tested in radial arm maze to assess the learning and memory performance. Based on these results, mice were treated orally with 200 mg/kg of C. asiatica for 15 days from day 15 to day 30 post partum (p.p.) and the nootropic effect was evaluated on the 31st day and 6 months p.p. The behavioral (open field, dark/bright arena, hole board and radial arm maze tests), biochemical (acetylcholine esterase activity) and histological studies (dendritic arborization) were carried out. Performance of juvenile and young adult mice was significantly improved in radial arm maze and hole board tests, but locomotor activity did not show any change compared to control. Treatment resulted in increased acetylcholine esterase activity in the hippocampus. Dendritic arborization of hippocampal CA3 neurons was also increased in terms of intersections and branching points, both at one month and 6 months. Results of the present investigation show that treatment during postnatal developmental stage with C. asiatica extract can influence the neuronal morphology and promote the higher brain function of juvenile and young adult mice.

Possible role of glutathione in predicting radiotherapy response of cervix cancer.

PURPOSE: To see if changes in tumor/blood glutathione (GSH) levels after one fraction of radiotherapy can be correlated with the treatment response in patients with carcinoma of the uterine cervix. METHODS AND MATERIALS: The study was done on 45 patients with squamous cell carcinoma of the uterine cervix, FIGO Stages IIB (17 patients) and IIIB (28 patients). Stage IIB patients received 35 Gy of cobalt-60 external radiotherapy (RT) in 16 fractions over 4 weeks with a concurrent high-dose-rate intracavitary dose of 8.5 Gy to point A once a week. Stage IIIB patients were given 45 Gy of RT in 20 fractions over 5 weeks, followed by two doses of intracavitary therapy once a week. Blood and tumor samples were collected before and after one dose of RT and GSH was estimated. Tumor response was assessed clinically at 1 month after treatment. RESULTS: Glutathione levels in both blood and tumor showed a significant decrease after one fraction of RT, but the degree of decrease varied among patients. There was a good correlation between the extent of GSH decrease and the tumor response. All patients who had complete response (CR) (seven Stage IIB and eight Stage IIIB) showed > or =70% decrease in both tumor and blood GSH, while those who had <50% regression (NR) (five Stage IIB and 13 Stage IIIB) showed <50% decrease in GSH. The partial responders recorded an intermediate level (50-70%) of depletion in blood and tumor GSH. CONCLUSIONS: The results indicate that the changes in tumor/blood GSH levels after one fraction of RT could serve as an index of tumor response to therapy and may help in identifying radioresistant tumors, at least in the case of cervix carcinoma.

Radioprotective effect of combinations of WR-2721 and mercaptopropionylglycine on mouse bone marrow chromosomes.

The radioprotective and toxic effects of low to moderate doses of S-2-(3-aminopropylamino)ethyl phosphorothioic acid (WR-2721) and its combination with mercaptopropionylglycine (MPG, 20 mg/kg body wt) on the chromosomes of the bone marrow cells of Swiss albino mice were studied at 24 h and 14 days postirradiation. Significant protection against radiation-induced chromosome aberrations was observed with 50 mg/kg WR-2721. The protection increased with the dose of the drug administered, and the degree of protection per unit dose increment was more pronounced at lower than at higher doses. A combination of WR-2721 and MPG given before exposure resulted in a significantly greater number of normal metaphases at 24 h postirradiation compared to the respective single-drug treatment groups. On Day 14 postirradiation, when the presence of WR-2721 resulted in an increase in the frequency of aberrant cells, combination with MPG helped to reduce this value markedly, especially at WR-2721 doses below 200 mg/kg. On the basis of these results it is suggested that 150 mg/kg WR-2721 may be considered an optimum dose for combination with MPG for protection of chromosomes of bone marrow cells when repeated drug administrations are not needed. Changes in the level of glutathione (GSH) in the blood were studied at different times following the administration of 150 mg/kg WR-2721 and its combination with MPG (20 mg/kg) before sham irradiation or exposure to 4.5 Gy 60Co gamma rays. The results showed that WR-2721 elevated blood GSH levels significantly above normal values by the time radiation was delivered, while MPG did not. Glutathione appears to have an important role in the action of WR-2721, while protection by MPG may not be mediated through GSH. Injection of MPG after WR-2721 helps to maintain the higher GSH level for a longer duration compared to treatment with WR-2721 alone. It is possible that MPG delays the metabolism of GSH.

Modification of WR-2721 radiation protection from gastrointestinal injury and death in mice by 2-mercaptopropionylglycine.

The radioprotective efficiency of S-2-(3-aminopropylamino)-ethyl phosphorothioic acid (WR-2721) and 2-mercaptopropionylglycine (MPG) was studied in Swiss albino mice exposed to whole-body gamma irradiation (15.0 Gy). WR-2721 (150 mg/kg), an optimum dose of MPG (20 mg/kg), or a combination of the two was administered intraperitoneally before irradiation. The radiation protection was assessed on the basis of histological changes in the jejunal mucosa on Day 3 postirradiation, development of gastrointestinal (GI) syndrome, and animal survival. In the irradiated control the number of surviving crypts was reduced to less than 17% of the value for sham-irradiated mice, and there was a complete collapse of villi. Treatment with MPG resulted in survival of about 35% of the crypts, but no notable protection of the villus structure was evident. WR-2721 alone or in combination with MPG protected both crypts and villi. The combination treatment increased the crypt cellularity and villus height significantly. The changes in the intestinal mucosa were directly correlated with the GI syndrome and death. Irradiation in the absence of the protectors resulted in 100% mortality in 10 days preceded by the signs of severe GI syndrome. Each drug individually delayed the onset of radiation sickness and reduced the severity of the signs. While MPG was not able to increase the survival rate of the animals above that of the controls, WR-2721 increased the survival rate at 10 days to 70% and at 30 days to 30%. The combination of WR-2721 with MPG further reduced the death rate from damage to the GI tract, resulting in 95% survival on Day 10; no signs of radiation sickness were noted in these animals. This treatment also increased the 30-day survival to 70%. The combination of the drugs is seen to be superior to the single-drug treatments in reducing GI injury and increasing survival.

In vivo postirradiation protection by a vitamin E analog, alpha-TMG.

The water-soluble vitamin E derivative alpha-TMG is an excellent radical scavenger. A dose of 600 mg/kg TMG significantly reduced radiation clastogenicity in mouse bone marrow when administered after irradiation. The present study was aimed at investigating the radioprotective effect of postirradiation treatment with alpha-TMG against a range of whole-body lethal (8.5-12 Gy) and sublethal (1-5 Gy) doses of radiation in adult Swiss albino mice. Protection against lethal irradiation was evaluated from 30-day mouse survival and against sublethal doses was assessed from micronuclei and chromosomal aberrations in the bone marrow 24 h after irradiation. An intraperitoneal injection of 600 mg/kg TMG within 10 min of lethal irradiation increased survival, giving a dose modification factor (DMF) of 1.09. TMG at doses of 400 mg/kg and 600 mg/kg significantly reduced the percentage of aberrant metaphases, the different types of aberrations, and the number of micronucleated erythrocytes. DMFs of 1.22 and 1.48 for percentage aberrant metaphases and 1.6 and 1.98 for micronuclei were obtained for 400 mg/kg and 600 mg/kg TMG, respectively. No drug toxicity was observed at these doses. The effectiveness of TMG when administered postirradiation suggests its possible utility for protection against unplanned radiation exposures.

In vivo radioprotection by ocimum flavonoids: survival of mice.

Two flavonoids, orientin and vicenin, isolated from the leaves of the Indian plant Ocimum sanctum were tested for their radioprotective effect in mice. Both compounds provided protection against death from gastrointestinal syndrome as well as bone marrow syndrome when injected intraperitoneally (i.p.) before whole-body exposure to 11 Gy gamma radiation. The optimum drug dose for protection was 50 microg/kg body weight: An increase in the drug dose did not increase protection. No acute toxicity was observed at doses as high as 100 mg/kg body weight of either compound. Maximum protection was obtained when either compound was injected i.p. 30 min before irradiation. Changing the route of administration or the interval between drug injection (i.p.) and irradiation reduced protection. Drug treatment after irradiation was not very effective. Vicenin was slightly better than orientin in increasing survival at 30 days; protection by vicenin also lasted longer. Dose modification factors (DMFs) for the LD50 were 1.37 for vicenin and 1.30 for orientin. Radical scavenging activity has been demonstrated for both orientin and vicenin, and this appears to be one of the mechanisms of protection by these flavonoids.

Radiation protection by the ocimum flavonoids orientin and vicenin: mechanisms of action.

In previous studies, flavonoids, orientin and vicenin, that were isolated from the leaf extract of Ocimum sanctum, were found to protect mice against radiation injury. Several flavonoids are known to be good antioxidants. Therefore, the effect of orientin and vicenin on radiation-induced lipid peroxidation in vivo and their antioxidant activity in vitro were studied. Adult mice were injected intraperitoneally with 50 microgram/kg of orientin or vicenin and exposed whole-body to 3 Gy of gamma radiation. Lipid peroxidation was measured in the liver 15 min to 8 h postirradiation. The antioxidant activity of orientin/vicenin (10-500 microM) was studied by measuring inhibition of hydroxyl radicals generated by the Fenton reaction (Fe(3+)-EDTA-ascorbic acid-H(2)O(2)) in vitro. The compounds were also tested for possible pro-oxidant and iron chelation activities at the above concentrations in the in vitro system. Orientin and vicenin provided almost equal protection against radiation-induced lipid peroxidation in mouse liver. Both compounds showed a significantly greater free radical-inhibiting activity in vitro than DMSO. Neither orientin nor vicenin showed any pro-oxidant activity at the concentrations tested. Both compounds inhibited free radical formation in the absence of EDTA. Free radical scavenging appears to be a likely mechanism of radiation protection by these flavonoids.

Tissue Raman spectroscopy for the study of radiation damage: brain irradiation of mice.

Radiotherapy is routinely employed in the treatment of head and neck cancers. Acute cell death, radiation-activated chemical cascades, and the induction of genes coding for protective factors like cytokines are considered to be the major processes involved in radiation damage and repair. It should be possible to follow these processes by monitoring the biochemical interactions initiated by radiation. We have carried out Raman spectroscopy studies on tissue from mice subjected to brain irradiation to identify the biochemical changes occurring in tissue and brain as a result of radiation injury. These studies show that brain irradiation produces drastic spectral changes even in tissue far removed from the irradiation site. The changes are very similar to those produced by the stress of inoculation and restraint and the administration of an anesthetic drug. While the changes produced by stress or anesthetics last for only a short time (a few hours to 1 or 2 days), radiation-induced changes persist even after 1 week. The spectral changes can be interpreted in terms of the observation of new spectra that are dominated by bands due to proteins. The results thus support the hypothesis that various protective factors are released throughout the body when the central nervous system (CNS) is exposed to radiation.

Long-term effects of diagnostic ultrasound during fetal period on postnatal development and adult behavior of mouse.

Pregnant Swiss albino mice were exposed to diagnostic levels of ultrasound (3.5 MHz, intensity 65 mW, I(SPTP) = 1 W/cm(2), I(SATA) = 240 W/cm(2)) for 10, 20 and 30 minutes on day 14 of gestation. Sham exposed controls were maintained for comparison. Fifteen pregnant mice were exposed for each group. Exposed as well as control animals were left to complete gestation and parturition. Ultrasound induced changes in maternal vaginal temperature was recorded. The changes in the physiological reflexes and postnatal mortality up to 6 weeks of age were recorded. The litters were subjected to behavioral tests for locomotor activity, learning and memory at 4 month and 1 year of age. Neither the physiological reflexes nor the postnatal mortality was affected by ultrasound exposure. However, there was a noticeable impairment in both locomotor and learning behavior even after a 10 min exposure, which further increased with increases in exposure time. Thus the present study demonstrates the neurotoxicity of diagnostic ultrasound and the high susceptibility of early fetal brain to induction of lasting detrimental changes by ultrasound exposure.

Protection against prenatal irradiation-induced genomic instability and its consequences in adult mice by Ocimum flavonoids, orientin and vicenin.

PURPOSE: To study the protective effect of orientin and vicenin against early genomic effects of foetal irradiation and their late consequences in mice. MATERIALS AND METHODS: Fourteen-day pregnant mice were exposed to 1 Gy 60Co gamma-radiation 30 min after an intraperitoneal injection of orientin or vicenin (50 microg kg(-1) body weight). Chromosomal aberrations were studied in foetal liver cells and their spleen colonies (three passages, colony-forming units-spleen CFU-S1, CFU-S2, CFU-S3) and 1-12 months post-partum bone marrow. Peripheral blood counts and solid tumours were recorded to 12 and 20 months, respectively. RESULTS: Irradiation significantly increased the percent aberrant cells and aberrations/cell in foetal liver and CFU-S1. These effects decreased in later passages of CFU-S and were not seen at 1-6 months post-partum, but increased significantly from 9 months. Total blood counts showed significant reduction from 6 months, while neutrophils increased from 3 months post-partum. Solid tumour incidence in adults increased significantly, with a decrease in age at detection. Orientin/vicenin significantly reduced the chromosomal anomalies in foetal and adult haemopoietic cells, restored blood counts to the normal range, and significantly reduced tumour incidence and delayed tumour development to control age. CONCLUSIONS: Orientin and vicenin protect against foetal irradiation-induced genomic damage and instability, thereby reducing the delayed chromosomal abnormalities and tumorigenesis in adult.

Mouse bone-marrow response to low doses of whole-body gamma irradiation: induction of micronuclei.

The induction of micronuclei in mouse bone marrow was studied after whole-body exposure to low doses of gamma radiation, ranging from 5 to 75 cGy. Micronuclei were scored at 10 and 30 h after irradiation. A linear dose response was obtained at both postirradiation times. However, the number of micronuclei per 100 nuclei was lower at 30 h than at 10 h, and the dose-response curve for the former had a shallower slope. When fitted to the alpha D + beta D2 model, a negative beta value was obtained. This could be due to division delay, combined with elimination of damaged cells by death at higher doses.

Effect of irradiation at the early fetal stage on adult brain function in the mouse: locomotor activity.

PURPOSE: To study long-term changes in the adult locomotor activity of mice after exposure to gamma radiation at the early fetal stage of development. MATERIALS AND METHODS: Pregnant Swiss albino mice were exposed locally on the abdominal area to a single dose of 0.25-1.5 Gy of 60Co gamma radiation at the dose rate of 1 Gy/min. When the F1 offspring were 6 months old, their locomotor and exploratory behaviour was assessed by the open-field and dark/bright arena tests. Animals were again subjected to the dark/bright arena test at 12 and 18 months of age in order to study the persistence of the effects. RESULTS: Irradiation produced a noticeable disturbance in the normal behaviour pattern of the mice. There was a significant dose-dependent decrease in the open-field activity of 6-month-old mice. In the dark/bright arena test, the time spent and lines crossed in the dark area showed a significant decrease, while their activities in the brightly lit area increased significantly, indicating a reduced aversion to bright light. These effects were evident even at a dose of 0.3 Gy and increased linearly with dose. The significant behavioural changes persisted at 12 months, but at 18 months the difference in the time spent and lines crossed in the dark and bright areas were not significantly different from sham-irradiated control values below 0.5 Gy. CONCLUSIONS: These results show that day 14 of gestation in Swiss albino mice is a time of high risk for inducing long-term changes in the adult locomotor function by gamma-radiation doses below 1 Gy. Using a range of radiation doses and different observation times we have demonstrated that the effect increases linearly with dose, but there appears to be a threshold of 0.3-0.5 Gy for producing significant persistent changes in the adult ambulatory activity.

Effect of irradiation at the early foetal stage on adult brain function of mouse: learning and memory.

PURPOSE: To study the long-term effect of early foetal irradiation on the learning and memory in the adult mouse. MATERIALS AND METHODS: The abdominal area of pregnant Swiss albino mice was exposed to a single dose of 0.25-1.5Gy gamma-radiation on the 14th day of gestation and the mice were left to deliver their offspring. At 6 months of age, the learning and memory functions of the F(1) mice were tested by hole-board activity, conditioned avoidance response and radial arm maze performance. The animals were again subjected to the radial arm maze test at 12 and 18 months of age. RESULTS: There was a significant dose-dependent decrease in the learning ability and memory retention of 6-month-old mice at doses > 0.25Gy. The significant changes persisted to 18 months of age in mice exposed to >or= 0.5Gy. All changes showed a linear dose-response at doses < 1Gy. CONCLUSIONS: The gestational day 14 of Swiss albino mice is a sensitive stage in brain development to gamma-ray-induced impairment of learning and memory during the adult life. Permanent deficits in these functions can be induced by a dose of approximately 0.5Gy at this stage, when the developmental activity of the cerebral cortex is at its peak.

Induction of solid tumours in the Swiss albino mouse by low-dose foetal irradiation.

PURPOSE: To study the tumourigenic effect of prenatal low-dose gamma-irradiation in the mouse. METHODS AND MATERIALS: Pregnant Swiss albino mice were exposed to 0.1-1.5 Gy gamma-radiation on days 14 or 17 of gestation. The F1 offspring were observed up to 18 months of age. All the mice were killed at 18 months and the incidence of tumours in different organs was recorded. RESULTS: Exposure to doses from 0.1 to 1.5 Gy on days 14 or 17 of gestation produced a linear-quadratic dose-dependent increase in tumour incidence in adult F1 mice. The main organs affected were the ovary, uterus, liver and spleen. The highest incidence was observed in the ovaries, which was significantly higher than spontaneous incidence, even at 0.25 Gy. In other organs the tumour incidence was not significant compared with controls at doses < 0.5-1.0 Gy. Tumours in the ovary and uterus developed at an earlier age than in the liver and spleen. CONCLUSIONS: Exposure to gamma-radiation < 1.0 Gy at the foetal period (days 14 or 17 of gestation) can cause induction of tumours in the Swiss albino mouse. The carcinogenic effect, particularly on the ovary among the female mouse, is detectable after low-dose foetal irradiation.