Differential Repair of O4-Methylthymine and O6-Methylguanine in Rat and Hamster Liver

Self-destruction and tolerance in resistance of mammalian cells to alkylation damage

“…Recently some light has been shed on this apparent paradox by the interesting observation (25,26) (34,35) to show that the increased enzyme activity in rat (but not a human) hepatoma lines is correlated with an increased steady-state level of MGMT mRNA, indicating that the response might be controlled at the level of MGMT transcription. Significantly, hamsters (which are extremely sensitive to tumor induction by dimethylnitrosamine) are unable to replace the hepatic MGMT molecules depleted during repair whereas rapid recovery (induction) to beyond pretreatment levels is initiated within 24hr in rat liver (36). More recently, it has been shown that induction of MGMT activity in rat liver by treatment with nitrosamines is also associated with a higher steady-state level of MGMT mRNA, although the levels of other, unrelated mRNAs are also increased (J.…”