[Cross-adaptation as affected by methylating and ethylating compounds and mitomycin c]

The present study examines cross-adaptation between alkylating agents and antibiotic mitomycin C (MC). Ethylating and methylating agents induce monoadducts in DNA in the form of ethyl and methyl radicals. MC induces DNA cross-links. In our experiments on cross-adaptation, low concentration of ethylenimine (EI) did not induce an adaptive response following posttreatment with methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (NG) at mutagenic concentration. Pretreatment with low EI concentration and posttreatment with MC did not induce adaptive response to late fixation. Pretreatment with NG at low concentration and subsequent posttreatment with EI at high concentration reduced the yield of chromosomal aberrations (adaptive response), compared to the effect of EI alone. Adaptive response is absent when pre- and posttreatment are performed within phase G1, and the effect of sensibilization is noted in this case. After posttreatment with MC at mutagenic concentration, the adaptive response is expressed in the case of increased cell-cycle duration. Posttreatment with MC at low mutagenic concentration did not lead to any adaptive response following NG pretreatment. In experiments with low MC concentration and posttreatment with high EI concentrations, 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 agent NG, and ethylating agent EI despite differing damage to DNA. This effect is dependent on the character of DNA damage following pretreatment, concentration and character of the mutagen used for posttreatment, and the duration and phase of the cell cycle.