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O6-Methylguanine-DNA methyltransferase (O6-MT) has been described as a DNA repair enzyme that reverses alkylation damage at the O6 position of guanine in DNA. We demonstrate that the concentration of this protein decreases immediately prior to DNA synthesis in cultured chick hepatocytes. If intracellular levels are experimentally depleted by treatment of cultures with O6-methylguanine, DNA synthesis occurs as an associated resultant. This effect is dose dependent and can be followed by discernible morphological changes of organoids in culture. Increased and altered growth caused by O6-methylguanine was quantified and was also found to be dose dependent. Therefore, O6-MT may play a role in the regulation of DNA synthesis.

O6-Methylguanine-DNA methyltransferase (O6-MT) is a DNA repair protein that reverses alkylation damage at the O6 position of guanine. In the process, O6-MT undergoes suicide inactivation. To determine if this enzyme might be regulated by pregnancy-associated hormones we measured changes in the level of O6-MT in isolated mouse mammary epithelial cell homogenates during different reproductive states. These were pregnancy, ectopic pituitary transplantation, proestrus/estrus and diestrus. O6-MT levels were found to be similar in mice in proestrus/estrus (0.95 fmol/micrograms DNA) as compared to diestrus (0.94 fmol/micrograms DNA) and also mixed populations of virgin mice (1.09 fmol/micrograms DNA). A mean for all virgin mice (0.97 fmol/micrograms DNA) was used as a comparative index. O6-MT decreased 2-fold during pregnancy in mammary epithelial cells to a mean value of 0.45 fmol/micrograms DNA (P less than 0.05). A smaller decrease (0.65 fmol/micrograms DNA; P less than 0.01) in mammary epithelial cells was found at 3 weeks following pituitary isograft. The repair capacity of mammary epithelial cells to liver was compared by measurements made in liver homogenates from the same mice and are approximately 3-fold higher in liver from virgin mice (3.2 fmol/micrograms DNA) than mammary gland. Liver levels of O6-MT increased in pregnant (5.3 fmol/micrograms DNA) and pituitary transplanted (3.9 fmol/micrograms DNA) mice, and were 5- and 4-fold higher than the concentration in virgin mammary epithelial cells respectively.

O6-Methylguanine methyltransferase (O6-MT) was measured and compared in extracts of 7 human fetal tissues obtained from 21 different fetal specimens as a function of fetal age and race and of maternal smoking and drug usage. Liver exhibited the highest activity followed by kidney, lung, small intestine, large intestine, skin, and brain. Each fetal organ homogenate exhibited a 3- to 5-fold level of interindividual variation of O6-MT. There did not appear to be any significant differences of O6-MT as a function of fetal race and age and in the tissues obtained from mothers who smoked cigarettes during pregnancy. The fetal tissues obtained from an individual using phenobarbital exhibited 4-fold increases in O6-MT activity. The tissues obtained from another individual on kidney dialysis were 2- to 3-fold higher than the normal population. These data suggest a possible enhancement of human fetal O6-MT by certain xenobiotics, with little if any modulation by racial factors and maternal smoking habits.