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.