CROSS-ADAPTATION INDUCED BY METHYLATING A ND ETHYLATING AGENTS AND MITOMYCIN-C

The present study examines cross-adaptation between alkylating agents and antibiotic mitomycin C(MC). Ethylating and methylating agents indu ce monoadducts in DNA in the form of ethyl and methyl radicals, MC ind uces DNA cross-links. In our experiments on cross-adaptation, low conc entration of ethylenimine (EI) did not induce an adaptive response fol lowing posttreatment with methylating agent N-methyl-N'-nitro-N-nitros oguanidine (NG) at mutagenic concentration. Pretreatment with low EI c oncentration and posttreatment with MC did not induce adaptive respons e to late fixation. Pretreatment with NG at low concentration and subs equent posttreatment with EI at high concentration reduced the yield o f chromosomal aberrations (adaptive response), compared to the effect of EI alone. Adaptive response is absent when pre- and posttreatment a re performed within phase G(1), and the effect of sensibilization is n oted in this case. After posttreatment with MC at mutagenic concentrat ion, the adaptive response is expressed in the case of increased cell- cycle duration. Posttreatment with MC at low mutagenic concentration d id not lead to any adaptive response following NG pretreatment. In exp eriments with low MC concentration and posttreatment with high EI conc entrations, the adaptive response was observed, whereas in experiments with NG posttreatment, an increased yield of aberrations (the effect of sensibilization) was observed. Thus, in cross-adaptation, inducible repair, i.e., adaptive response, is demonstrated by MC, methylating a gent NG, and ethylating agent EI despite differing damage to DNA. This effect is dependent on the character of DNA damage following pretreat ment, concentration and character of the mutagen used for posttreatmen t, and the duration and phase of the cell cycle.