Lack of effect of glutathione on the binding of dimethylnitrosamine to DNA in vitro.

The possibility that glutathione (GSH) S-transferases may affect microsome-mediated methylation of DNA by dimethylnitrosamine (DMN) in vitro has been investigated using aflatoxin B1 (AFB1) as a positive control. Hamster liver microsomes were incubated with either [14C]DMN or [3H]AFB1 and calf thymus DNA, with or without GSH and hamster cytosol. Although a significant amount of DMN was metabolized, GSH alone or in conjunction with cytosol or purified GSH S-transferases did not affect the binding of 14C to DNA and the amount of 7-methylguanine formed. However with AFB1, a significant reduction in both its binding to DNA and in the formation of AFB1-N7Gua adduct with a concomitant increase in AFB1-GSH conjugation was observed, suggesting that the test system was functioning effectively.