Combination Of Gamma Irradiation Research Articles

Gamma radiolysis of alachlor aqueous solutions in the presence of hydrogen peroxide

The enhanced effect of gamma irradiation with hydrogen peroxide (H2O2) for alachlor degradation in an aqueous solution was first investigated in this study. The combination of gamma irradiation and H2O2 led to an enhanced effect, which remarkably increased the degradation efficiency of alachlor and the total organic carbon (TOC) removal. At a dose of 200Gy, the degradation degree of the alachlor solution reached 81.7 and 99.2% under H2O2 concentrations of 0 and 0.1μM, respectively. In addition, the TOC removal efficiencies of the alachlor under initial H2O2 concentrations of 0, 0.5 and 1.0μM were 59.5, 74.8 and 83.8%, respectively, at an absorbed dose of 20kGy. However, for higher H2O2 concentrations (greater than 1μM), the alachlor degradation was reduced because OH radicals were scavenged by the H2O2. The biodegradability of alachlor solutions prior to and after treatment by gamma irradiation was also assessed using the Closed Bottle Test (CBT). The results showed enhanced biodegradability of alachlor with increasing absorbed doses.

키토산 코팅 및 감마선 조사에 의한 계란에 오염된 위해 미생물 제어 및 영양학적 특성 평가

The effect of combination of chitosan coating and gamma irradiation on Escherichia coli inactivation and nutritional properties of shell egg was investigated. The E. coli inoculated on shell egg was not detected by 2 kGy of gamma irradiation at day 0 and/or chitosan coating (1%, pH 5.0) after 3 days of storage. There was no E. coli detected thereafter. In the contents of moisture, crude fat, crude protein, ash, retinol, phospholipid, and minerals, no difference was found by treatment combination. However, the contents of cholesterol and carotenoids were reduced by irradiation of 2 kGy (P<0.05). Results suggest that the combination of gamma irradiation (2 kGy) and chitosan coating (1%) can be a good method to improve the safety and prolonged

Effect of integrated application of gamma irradiation and modified atmosphere packaging on physicochemical and microbiological properties of shiitake mushroom (Lentinus edodes)

Abstract Shiitake ( Lentinula edodes ) mushrooms were packed in biorientated polypropylene (BOPP) bags and exposed to different doses of gamma irradiation (1.0, 1.5, and 2.0 kGy) within the packaging, heat sealed and stored at 4 °C for 20 d. Of the three doses, 1.0 kGy was most effective in maintaining a high level of firmness. Samples treated with 1.0 kGy also exhibited smaller initial declines in soluble protein, higher increases in total sugar content and lower levels of malondialdehyde accumulation. Furthermore, 1.0 kGy promoted the accumulation of phenolics compound and showed higher antioxidant ability during storage. At higher doses, 2.0 kGy resulted in a higher microbial reduction, but showed negative effects on texture, chemical properties and functional components. All the gamma irradiation were effective in retarding mushroom sensory deterioration. Thus, application of gamma irradiation in combination with MAP can extend the storage life of shiitake mushroom up to 20 d.

감마선 조사와 푸코이단/라미나린 병용처리가 돈육 패티의 품질에 미치는 영향

저급미역에서 추출한 푸코이단/라미나린의 천연 항산화제로서의 이용 가능성을 평가하기 위해 돈육 패티에 이를 첨가하여 품질평가를 하였다. 푸코이단/라미나린 첨가 돈육 패티의 지질산패도를 측정한 결과 무첨가구에 비해 효과적으로 패티의 지질산화를 억제한 것으로 나타났으며, 이는 조사선량에 따라 지질산화 억제 효과가 증진하였다. 감마선 조사한 돈육 패티의 색도 변화를 측정한 결과, 시료 무첨가구와 라미나린 첨가구는 조사에 의한 유의적인 차이는 없었으나 푸코이단 처리구의 경우 패티의 조사선량이 증가함에 따라 명도가 증가하는 경향을 보였다. 돈육 패티에 푸코이단/라미나린을 첨가 하였을 때 패티의 보수성이 증가하여 경도가 감소하였으며, 이는 감마선 조사에 의한 유의적인 차이는 없는 것으로 나타났다. 그리고 감마선 조사와 푸코이단/라미나린 병용처리는 패티의 미생물을 제어하는 것으로 나타났다. 본 연구 결과 감마선 조사와 이 기술을 활용하여 추출한 푸코이단/라미나린을 병용처리 하였을 때 미생물학적 안전성을 확보하고 품질을 개선시켜 식품산업에서의 천연 항산화제로서 적용할 수 있을 것이라고 판단된다. The objective of this study was investigated to apply the fucoidan and laminarin extract from low-grade Undaria pinnatifida to real food product, a pork patty. Pork patties added with fucoidan and laminarin showed lower lipid oxidation and the inhibition against lipid oxidation was shown to be dependent on the irradiation doses. The Hunter color values of pork patty added with fucoidan increased significantly with an increase of irradiation dose. The hardness profiles of the patties with fucoidan and laminarin was decreased, but the amount of water in the patties was increased. Also, the combination of gamma irradiation and addition of fucoidan and laminarin was shown to be effective for the microbiological control. These results suggested that gamma irradiation and fucoidan and laminarin treatment showed the positive effect on microbial stability and quality of the pork patty.

Effect of Irradiation on Microbial Safety and Nutritional Quality of Minimally Processed Bitter Gourd (Momordica charantia)

ABSTRACT: The feasibility of gamma radiation in combination with low temperature was studied to ensure microbiological safety and maintaining physicochemical and sensory characteristics of minimally processed bitter gourd. Radio sensitivity (D10 values, that is, irradiation dose required for 90% reduction of microorganisms) for Salmonella paratyphae A and Escherichia coli were 0.28 kGy and 0.23 kGy, respectively. On the basis of D10 values, 5D10 values were determined and samples of minimally processed bitter gourd were irradiated up to 5D10 values, stored for 14 d at 5 ± 1 °C, and analyzed for total bacterial, fungal, and coliform counts. Ascorbic acid, acidity, texture, and sensory qualities were also studied. Results showed that an irradiation dose of 2.0 kGy significantly reduced the microbial count to keep the samples microbiologically safe for 7d. Sensory evaluation revealed that the samples received maximum scores for appearance and flavor (7.8 and 7.9, respectively) with radiation dose of 2.0 kGy and minimum score for control (6.5). Firmness and ascorbic acid content decreased significantly with increase in storage time and irradiation dose. All the samples were discarded during the 2nd wk of storage due to high bio‐burden.

A combination of gamma irradiation and CaCl 2 immersion for a pectin-based biodegradable film

Using citrus pectin a biodegradable film was prepared by a combination treatment of gamma irradiation (0, 10, 20, and 30 kGy) and CaCl 2 immersion (0, 5, and 10%) cross-linking. The tensile strength of the pectin-based film was the highest in the 5% CaCl 2 treatment at 20 kGy of an irradiation dose. The tensile strength of the film with CaCl 2 was generally higher than that of the non-CaCl 2 treatment. The elongation at break and water vapor permeability were the lowest at a CaCl 2 of 5% among the irradiated treatments. The total organic carbon content produced from the Paenibacillus polymyxa and Pseudomonas aeruginosa showed that the film of the 20 kGy-irradiated film was lower than those of the 0, 10, and 30 kGy-irradiated films. In conclusion, irradiation of the film casting solution at 20 kGy combined with a 5% CaCl 2 immersion resulted in film with improved mechanical properties and biodegradability.

Potential of radiosensitizing agents in cancer chemo-radiotherapy

Potential of herbs and other plant-based formulations have been increasingly recognized in prevention and treatment of human diseases including cancer. There exist enormous prospect for screening and evaluation of herbal/plant products for developing effective radiosensitization and radioprotection relevant to nuclear research program. Investigations in our laboratory have focused on the mechanism of activity of variety of anticancer and antioxidant agents, namely, Eugenol, (EU), Ellagic acid (EA), Triphala (TPL), Tocopherol Succinate (TOS) and Arachidonic acid on normal and cancer cells with view to design effective protocols in practical radioprotection and cancer radiotherapy. This paper is mainly focused on studies on cytotoxic effects on cancer cell lines. Results have shown that these agents produced radiosensitizing action involving oxidative damage, membrane alteration and damage to nucleic acid in various human cell lines. Studies were performed employing fluorescence probes and electron spin resonance methods and gel electrophoresis protocols. It has been found that cytotoxic effect was induced by initiating membrane oxidative damage and by triggering intracellular generation of reactive oxygen species (ROS) by gamma radiation in combination with phytochemicals like TPL, EA and TOS in tumor cell line Ehrlich Ascites (EAC), Human cervical (HeLa) and breast (MCF-7) cells. Membrane damage and ROS generation was measured by DPH and DCF-FDA fluorescent probes respectively after exposure to low to moderate doses of gamma radiation. This talk will present the cytotoxic effects of phytochemicals in combination with ionizing radiation. It is emphasized that modulation of membrane peroxidative damage and intra cellular ROS may help achieve efficient killing of cancer cells which may provide a new approach to developing effective treatment of cancer.

DENDRITIC CELL BASED VACCINES: PROGRESS IN IMMUNOTHERAPY STUDIES FOR PROSTATE CANCER

No effective treatment is currently available for metastatic prostate cancer. Dendritic cell (DC) based cancer vaccine research has emerged from the laboratories to human clinical trials. We describe progress in the development of DC based prostate cancer vaccine. The literature was reviewed for major contributions to a growing number of studies that demonstrate the potential of DC based immunotherapeutics for prostate cancer. Background topics relating to DC based immunotherapy theory and practice are also addressed. DCs have been recognized as the most efficient antigen presenting cells that have the capacity to initiate naive T cell response in vitro and in vivo. During their differentiation and maturation pathways, dendritic cells can efficiently capture, process and present antigens for T cell activation. These characteristics make DC an attractive choice as the cellular adjuvant for cancer vaccines. Advances in DC generation, loading, and maturation methodologies have made it possible to generate clinical grade vaccines for various human trials. More than 100 DC vaccine trials, including 7 studies of patients with advanced prostate cancer have been reported to date. These vaccines were generally well tolerated with no significant adverse toxicity reported. Clinical responders have been identified in these studies. The new prospects opened by DC based vaccines for prostate cancer are fascinating. When compared to conventional treatments, DC vaccinations have few side effects. Improvements in patient selection, vaccine delivery strategies, immune monitoring and vaccine manufacturing will be crucial in moving DC based prostate cancer vaccines closer to the clinics.

Combination of minimal processing and irradiation to improve the microbiological safety of lettuce ( Lactuca sativa, L.)

The feasibility of gamma radiation in combination with minimal processing (MP) to reduce the number of Salmonella spp. and Escherichia coli O157:H7 in iceberg lettuce ( Lactuca sativa, L.) (shredded) was studied in order to increase the safety of the product. The reduction of the microbial population during the processing, the D 10-values for Salmonella spp. and E. coli O157:H7 inoculated on shredded iceberg lettuce as well as the sensory evaluation of the irradiated product were evaluated. The immersion in chlorine (200 ppm) reduced coliform and aerobic mesophilic microorganisms by 0.9 and 2.7 log, respectively. D-values varied from 0.16 to 0.23 kGy for Salmonella spp. and from 0.11 to 0.12 kGy for E. coli O157:H7. Minimally processed iceberg lettuce exposed to 0.9 kGy does not show any change in sensory attributes. However, the texture of the vegetable was affected during the exposition to 1.1 kGy. The exposition of MP iceberg lettuce to 0.7 kGy reduced the population of Salmonella spp. by 4.0 log and E. coli by 6.8 log without impairing the sensory attributes. The combination of minimal process and gamma radiation to improve the safety of iceberg lettuce is feasible if good hygiene practices begins at farm stage.

N-(4-hydroxyphenyl)retinamide (4-HPR) modulates GADD45 expression in radiosensitive bladder cancer cell lines

We previously demonstrated that N-(4-hydroxyphenyl)retinamide (4-HPR) and gamma-irradiation, when used in combination, had a synergistic effect in inducing apoptosis in bladder cancer cells, suggesting that 4-HPR may increase radiosensitivity in bladder cancer cells. To unravel molecular correlates in this radiosensitizing effect of 4-HPR, we examined the baseline and 4-HPR-induced expression of GADD45 to elucidate possible mechanisms by which 4-HPR enhanced the effect of gamma-irradiation in three bladder cancer cell lines. To investigate the role of p53 in mediating the radiosensitizing effect of 4-HPR, we also examined mutations in exons 5–9 by using direct sequencing and the levels of p53 expression by using RT-PCR and Western blot, before and after treatment with 4-HPR in these bladder cancer cell lines. Two cell lines had low expression of GADD45, and a dose-dependent increase in GADD45 expression induced by 4-HPR was found in bladder cancer cell lines without p53 mutations in exons 5–9. A combination of gamma-irradiation and 4-HPR showed a significantly greater effect in enhancing GADD45 expression than either agent used alone. The results indicate that the combined treatment with 4-HPR and gamma-irradiation has a stronger effect on GADD45 expression than the treatment with either agent alone, which suggests that the two agents may have an additive/synergistic effect. However, a normal p53 function appears to be necessary for the dose-dependent induction of GADD45 by 4-HPR. Once our results are verified and replicated by other investigators, 4-HPR may have a potential clinical implication in effectively treating bladder cancer in combination with low-gamma-irradiation therapy.

Performance Decrement after Combined Exposure to Ionizing Radiation and Shigella sonnei

Ionizing radiation could increase morbidity from common bacterial infections in military personnel on the modern battlefield. The combined effects of a sublethal dose of ionizing radiation and the bacterial diarrheal agent Shigella sonnei on body weight and forelimb grip strength in mice were assessed over a 30-day period. Individually housed B6D2F1 female mice were divided into four groups: control, sham irradiation + gavage with saline vehicle; 3 Gy 60Co gamma radiation at 0.4 Gy/min radiation + saline gavage; sham irradiation + 1.3 x 10(8) colony-forming units (CFUs) S. sonnei via gavage, administered 4 days postirradiation; and the combination of 3 Gy 60Co gamma radiation + 1.3 x 10(8) CFUs S. sonnei. Behavioral tests were conducted 3 days preirradiation and on days 9, 14, and 22 postirradiation. Body weight was significantly reduced in the radiation + Shigella group on days 5 to 10 postirradiation. Forelimb grip strength was reduced for mice in the radiation + Shigella group on days 9 and 14 postirradiation. These data demonstrate that an exposure to gamma radiation in combination with the bacterial agent S. sonnei can lead to a synergistic loss of body weight and degradation in performance.

DNA damage induced by gamma-radiation in combination with ethylene oxide or propylene oxide in human fibroblasts

To estimate the effects of interaction of gamma-rays and an epoxide, cell survival and induction of DNA double-strand breaks (DSBs) following combined exposure to ionizing radiation and ethylene oxide (EtO) or propylene oxide (PO) were studied in human fibroblasts. Two treatment protocols were applied: (a) the cells were pre-exposed to different doses of gamma-rays and then treated with epoxide, and (b) the cells were pretreated with epoxide and then exposed to different doses of gamma-rays. Here we show that order of the treatment did not play a role in cell survival and that the effect of combined exposure on cell killing was additive for both epoxides. As to DNA DSBs induction, however, a difference dependent upon the order of the treatment was observed. While EtO or PO treatment followed by gamma-rays exposure led to an increased number of DSBs at higher gamma-ray doses (2–3 Gy), no significant increase of DSBs was detected after the opposite order of the treatment (gamma-ray exposure followed by EtO or PO treatment).

Combination of gamma-irradiation and dendritic cell administration induces a potent antitumor response in tumor-bearing mice: approach to treatment of advanced stage cancer.

We investigated a new approach to the treatment of advanced stage cancer, a combination of apoptosis-inducing therapy and dendritic cell (DC) administration. MethA sarcoma and C3 tumor containing defined tumor-specific antigens in form of peptides' epitopes were selected as experimental mouse models. Sites of established subcutaneous tumors were gamma-irradiated with 10 Gy 3-5 times with 4-5 day interval. DCs generated from bone marrow of syngeneic mice were injected i.v. and s.c. after each irradiation. A large number of cell tracker-labeled DCs accumulated at the site of the irradiated tumor after s.c. injections. This effect was not observed in non-irradiated tumors. Almost all of these DCs bound GFP-labeled MethA cells in tumor tissue. Interferon-gamma production by splenocytes in response to the tumor-specific MHC class I matched peptides was determined by ELISPOT assays. The combination of gamma-irradiation and DC administration, but not each of the treatments alone resulted in a significant increase in T cell response to the specific, but not to the control peptides. An increased proportion of tumor peptide-specific CD8(+)-cells was found only in that group of mice using staining with tetramers. DCs with defective presentation of antigen via MHC class I or MHC class II pathways were unable to induce peptide-specific T cell response. The combination of gamma-irradiation and DC administration but not each of the treatments alone resulted in a dramatic antitumor effect. A substantial proportion of mice completely rejected their tumors (80% in case of MethA sarcoma and 40% in case of C3 tumor). In the rest of the mice, tumor growth was notably suppressed or completely blocked. These data suggest that the combination of apoptosis-inducing therapy and DC administration may be an attractive approach to the treatment of advanced cancer.

Effect of combined gamma-irradiation and alkali treatment on cotton–cellulose

The influence of high-energy irradiation and sodium hydroxide treatment on the structure of cotton–cellulose was studied. The irradiation resulted in degradation of cellulose characterized by the decrease in the degree of polymerization (viscosimetry) and increase in the carbonyl content (FTIR, CO stretching band at 1740 cm −1 ). The treatment with NaOH after irradiation had no significant effect on these characteristics. However as it was shown by XRD and SEM that the transformation of the crystalline structure from cellulose I to cellulose II was observed at lower alkaline concentration when irradiation pretreatment was applied.

EFFECT OF SOLUBLE POLYLACTIC ACID IN COMBINATION WITH GAMMA RADIATION ON GROUND BEEF INOCULATED WITH E. COLI O157:H71

Ground beef was inoculated with E. coli O157:H7 and treated with gamma radiation with and without the incorporation of a 2% soluble polylactic acid solution (SPLA) and stored at 4C for up to 7 days. Frozen samples received an average maximum dose of 125 krads, at an average dose rate of 17.1 krads/h. The pH, water activity and moisture (%) were determined. A complete randomized block design with three replications was used to determine the effects of gamma radiation, SPLA, and gamma radiation in combination with SPLA. SPLA gave a maximum log reduction of E. coli O157:H7 populations of 0.70 log10 CFU/mL after 48 h at 4C. Gamma radiation reduced E. coli O157:H7 by 4.55 log10 CFU/mL. When SPLA and gamma radiation were combined, the cellular death of E. coli O157:H7 was not significantly increased by the presence of SPLA.

Gamma radiation and MC540 photosensitization of melanoma in the hamster's eye.

The purpose of this study was to evaluate the effects of cobalt-60 gamma-radiation and argon laser irradiation using injected merocyanine (MC540) as a photosensitizer on pigmented and non-pigmented Bomirski hamster melanomas growing in the eye. The animals were treated with one of four regimens, receiving gamma-irradiation only, photosensitization only, a combination of gamma-irradiation and photosensitization, or a combined time-fractionated treatment. Tumours were exposed to laser light 24 h after injection, when the photosensitizing dye concentration was highest. The degree of tissue damage was evaluated by observation of the area for necrosis, interruption of blood circulation, and the shape and dissemination of the tumour cells. Additionally, tumour growth was monitored through the measurement of tumour volume and also calculated from histological cross sections on the assumption that the tumour morphology is hemi-ellipsoidal. A single treatment of tumours by a combination of photodynamic therapy and ionizing radiation resulted in an additive effect, inhibiting tumour growth for 2-4 days. A time-fractionated treatment, given four times every 24 h, markedly delayed tumour growth for up to 6 weeks. The results indicate that MC540-mediated photodynamic treatment in combination with gamma-radiation exerts a significant therapeutic effect on a rapidly growing melanoma.

Effect of a combined gamma irradiation and parylene plasma treatment on the hydrolytic degradation of synthetic biodegradable sutures

The aim of this study was to alter the hydrolytic degradation property of synthetic absorbable suture fibers so that their mass loss would occur at a shorter time without significantly compromising their tensile strength loss profile. A two-step treatment concept (gamma-irradiation followed by Parylene plasma deposition) was introduced for achieving this aim. Vicryl and Maxon were used as the model compounds to test this new concept. After the treatment, the in vitro hydrolytic degradation properties of Vicryl and Maxon were evaluated by weight loss, tensile breaking strength, heat of fusion and melting temperature, intrinsic viscosity, surface wettability, and surface morphology. The results suggested that gamma-irradiation at a dosage level between 0.2-2.0 Mrad for Vicryl sutures and about 2.0 Mrad for Maxon sutures were the most effective dosages to accelerate the suture mass loss. The subsequent Parylene plasma deposition treatment statistically significantly improved the retention of tensile strength for both gamma-irradiated Vicryl and Maxon sutures and hence counteracted the undesirable gamma-irradiation induced acceleration of tensile strength loss. However, this second-step Parylene plasma treatment extended the suture mass loss to longer periods. These findings were consistent with the observed surface wettability, surface morphology, intrinsic viscosity, and thermal properties. A thin hydrophobic Parylene skin layer wrapped around a suture was responsible for the slower rate in mass and strength loss. This outer skin layer acted as a barrier to not only water but also degradation fragments.

Preliminary studies on radiation resistance of thermophilic anaerobic spores and the effect of gamma radiation on their heat resistance

D 10 values of gamma irradiated spores of Clostridium thermosaccharolyticum ATCC 7956 and Desulfotomaculum nigrificans ATCC 7946 in spent mushroom-compost infusion were 2.54 kGy and 2.20 kGy, respectively, i.e. in the same range as the radiation D 10 values of various mesophilic bacterial spores of much lower heat resistance than that of the thermophilic spores investigated. The combination of gamma irradiation with a subsequent heat treatment had a synergistic sporicidal effect which increased with increasing radiation doses. The heat sensitization of bacterial spores by irradiation seems to be decreasing with decreasing inherent heat resistance of various spore-formers. Heat sensitization of D. nigrificans spores by 2.5 kGy dose of gamma radiation could also be demonstrated when they were inoculated into cultivated mushrooms ( Agaricus bisporus). It was, therefore, concluded that radiation doses which inhibit after-ripening and senescence of harvested fresh mushrooms may also improve under specific conditions the efficacy of the heat preservation of canned mushrooms.

The Effect of Combined Treatment with Platinum Complexes and Ionizing Radiation on DNAin Vitro

The conformation of isolated calf-thymus DNA treated with cis-diamminedichloroplatinum(II) (cis-DDP) or its trans-isomer (trans-DDP) and gamma radiation in combination was investigated by means of differential pulse polarography and circular dichroism spectroscopy. The results revealed that combined treatment with antitumour active cis-DDP enhanced the extent of double-stranded distorted regions in DNA molecules. If irradiation preceded the platination, the combined effect was purely additive, while the reverse order of application of the two agents resulted in an increased effect over and above what may be expected from using the two modalities separately. These results were explained on the basis of the hypothesis that favours as a major mechanism of this combined effect the fixation by the binding of cis-DDP of DNA lesions introduced during radiation. Combined treatment with antitumour inactive trans-DDP resulted in the enhancement of single-stranded, denatured DNA yield. However, more extensive alterations in DNA conformation were observed if DNA was platinated after irradiation. The different effects of the combined treatments with cis- and trans-DDP were thought to be connected with the different destabilizing effects resulting from distinct conformational distortions induced by the two isomers.

Synergistic induction of altered hepatocyte foci by combined gamma radiation and diethylnitrosamine administered to neonatal rats.

To investigate mechanisms underlying the formation of carcinogen-induced altered hepatocyte foci, we histochemically examined the livers of 150-day-old rats that had been treated neonatally with single doses of gamma radiation (75, 150 or 300 rad, whole body) and i.p.-injected diethylnitrosamine (DEN, 0.15 mumol/g body wt) either separately or in combination. Three focus phenotypes, showing the elevated gamma-glutamyl transpeptidase [GG(+)] and/or the iron-exclusion [Fe(-)] histochemical marker(s) were quantitated through the use of serial frozen sectioning techniques and computer-assisted image analysis. DEN and gamma radiation each induced foci when given separately but total focus yield per cm3 of liver was more than 10-fold greater in DEN-treated than in irradiated rats and approximately 3-fold higher in females than in males. Combining the DEN and radiation treatments synergistically increased total focus yields for both sexes, although this response declined with increasing radiation dosage. For rats receiving DEN alone, the sex-dependent differential in total focus yield was due to the higher frequencies in females of the iron-excluding phenotypes [Fe(-) alone and Fe(-) + GG(+)]; the frequencies of foci showing only GG(+) were similar in both sexes. In contrast, the enhancement in total focus yield resulting from the combined DEN--radiation treatments was primarily a consequence of increases in the foci with GG(+) alone. The results suggest that (a) qualitatively different types of genetic damage (carcinogen-induced point mutations and radiation-induced rearrangements) may interact synergistically in the induction of phenotypically altered cells and (b) separate genetic loci are involved in the sex-mediated modulation of focus production and the synergistic enhancement of focus production by DEN--gamma radiation interactions.