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Cytogenetic analysis of the population of the Beskaragai district of the Semipalatinsk oblast adjacent to the territory of the nuclear test site was conducted by means of an ecological genetic questionnaire and cytogenetic examination of metaphase chromosomes. An increase in the total mutation level in the region was observed. The frequency of chromosome aberrations among the population of the Beskaragai district (3.2%) was statistically significantly (about 1.5 times) higher than the background levels in the clear regions (from 1 to 2%). Furthermore, the frequency of aberrations in adolescents was comparable with that in the adults. The spectrum of chromosome aberrations pointed to a significant contribution of radiation component to the mutagenesis.

Unscheduled DNA synthesis in human fibroblasts pretreated with natural and recombinant interferons was studied by scintillated radiometry. UDS was increased in fibroblasts pretreated 7 days before UV-irradiation. Newly synthesized proteins induced in cells after interferon treatment were compared with heat shock proteins.

Proteins induced in human fibroblasts after treatment of some antimutagens (interferon, p-aminobenzoic acid, heating and vaccinia virus infection) were identified by means of polyacrylamide gel electrophoresis (10-15%) followed by fluorography of the gel. Influenza virus proteins (A/WSN/33) were used as markers to determine the molecular weights of the new proteins. The results obtained suggest that interferon, p-aminobenzoic acid, heating and vaccinia virus infection induced proteins with mol. weights of 24 and 18 kD except the protein with 76 kD observed only after heating insult.

The alkaline elution method was used to study DNA breaks induced by the different mutagens in human cells. Normal fibroblasts and fibroblasts from patients with homocystinuria, deficient in gamma-type repair were shown to be resistant to gamma-radiation after the vaccinia virus infection. In both cell lines there was a decrease in the number of the mutagen-induced DNA breaks.

Protective properties of human interferons against physical and chemical mutagens have been described earlier. This work was aimed at detecting an optimum of protective action of interferons in human fibroblasts using two criteria: the number of single-strand DNA breaks formed and the index of DNA repair synthesis. The protective ability of interferon was shown to be expressed starting after 4 h of cells' pretreatment and proceeding through 40 h in experiments with N-methyl-N-nitro-N-nitrosoquanidin. The phenomenon of stimulation of DNA repair synthesis in human cells pretreated with interferon proceeded even after replating cells during 8 h in the experiments with UV irradiation.

DNA repair was explored in continuous cells withdrawn from gout patients. The data obtained were compared to those on primary cells (lymphocytes) from the same patients. Two continuous lines of fibroblasts obtained from the biopsy material of patients suffering from gout were examined for stability of reparation defects on long cell passage. The studies were made with 4 to 12 passages of patients' fibroblasts. The use of criteria reflecting certain stages of DNA repair (reparative synthesis of DNA, formation of induced DNA ruptures and their resynthesis during cell postincubation, reactivation and induced mutagenesis of measles vaccine virus in patients' cells) allowed confirmation of repair defect stability in gout patients' cells on their long passage. Based on the data on preservation of the repair defect on cell passage it is concluded that gout patients demonstrate the genetically determined impairment of the synthesis of DNA repair enzymes participating in the recovery of DNA impairments induced by UV radiation or UV mimetics.

Effects of native and recombinant interferons in normal and xeroderma pigmentosum (XP) human fibroblasts were studied. The criteria to evaluate the effects of interferons were: inhibition of replicative DNA synthesis, modification of replicative and unscheduled DNA synthesis in UV-irradiated cells. It was demonstrated that the level of inhibition of replicative DNA synthesis with interferons was dependent on proliferative status of cell cultures. The level of 3H-thymidine incorporation after stimulation of cell proliferation was increased in UV-irradiated normal fibroblasts pretreated with interferons. Interferon effect was not observed in XP cells. In cell cultures with low level of proliferation treatment with interferon resulted in inhibition of DNA replication and pronounced increase in the unscheduled DNA synthesis. In quiescent cells the effect of interferon on unscheduled DNA synthesis in UV-irradiated cells was not pronounced. In XP cells UV-irradiation induced low unscheduled DNA synthesis which was not modified by interferon.