Regulation of O6-methylguanine-DNA methyltransferase levels in rat liver and kidney.

It was found that rat kidney contains a protein similar to that previously described in rat liver which catalyzes the transfer of the methyl group from O6-methylguanine in DNA to a protein-bound cysteine residue. The amount of the renal O6-methylguanine-DNA methyltransferase was increased up to 2.5-fold during renal hypertrophy in response to unilateral nephrectomy or treatment with folic acid. These results indicate that the protein in kidney resembles that in rat liver which is known to be increased in response to a variety of hepatotoxins or to partial hepatectomy. The liver O6-methylguanine-DNA methyltransferase was reduced by hypophysectomy or thyroidectomy and could be increased by treatment with growth hormone or thyroxine. The level in the liver was considerably lower than the adult value in 1-day-old rats and increased to adult values by 14 to 21 days. At no time was the amount in the neonatal rat liver higher than in the adult, indicating that liver cell proliferation alone is not obligatorily coupled with an elevated methyltransferase level. The high sensitivity of neonatal rats to liver carcinogenesis by dimethylnitrosamine may be related to the high rate of cell proliferation and the lower capacity to repair O6-methylguanine.