Studies on adaptation of V79 Chinese hamster cells to low doses of methylating agents

Pretreatment of V79 cells with N-methyl-N'-nitro-N-nitroso-guanidine(MNNG) or N-methyl-N-nitrosourea (MNU) significantly reducedthe frequency of mutations (6-thio-guanine resistance) inducedby a challenge dose of these agents. Mutagenic adaptation canbe observed after exposure to pretreatment doses which haveno measurable toxic or cytogenetic effects, and which do notchange DNA synthesis as measured at the moment of challenge.The influence of pretreatment on challenge dose-induced cellkilling, chromosomal aberrations, and sister chromatid exchangeshas also been studied. The effect of the challenge with respectto these end points was not in the same way dependent on thepretreatment dose as the challenge dose-induced mutation frequency.Therefore it is concluded that mutagenic adaptation and adaptationwith respect to the other end points studied have no identicalunderlying causes.