Cellular levels of O6-methylguanine-DNA methyltransferase in mammary epithelial cells and liver from virgin, pregnant and pituitary grafted mice.

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.