DNA methylation during chronic administration of 1,2-dimethylhydrazine in a carcinogenic regimen.

Abstract

The formation and persistence of O6-methylguanine and 7-methylguanine in colon, kidney, and liver DNA were measured over a period of 25 weeks during 1,2-dimethylhydrazine (SDMH) carcinogenesis. Rats were given 14 weekly s.c. injections of 21 mg SDMH/kg body wt., and methylated guanines in DNA were determined quantitatively one week after each injection to measure the long-term accumulation of these aberrant bases. No accumulation of either base was seen in colon DNA, and no O6-methylguanine was seen to accumulate in liver DNA. The concentrations of O6-methylguanine and 7-methylguanine in kidney DNA did increase with reported administration of the carcinogen, but these bases were removed within six weeks after the last (14th) injection of SDMH. Large amounts of 7-methylguanine accumulated in liver DNA over the 14-week treatment period. The concentration of 7-methylguanine in liver and kidney DNA increased at rates greater than could be accounted for by using kinetic relationships determined in single-exposure studies. The concentration of O6-methylguanine in kidney DNA also increase at a rate greater than would be expected from calculations based on the rate of removal following a single administration of SDMH.

• Authors: D C Herron, R C Shank
• Journal: Carcinogenesis (Carcinogenesis) Vol. 3 Issue 8 Pg. 857-60 ( 1982) ISSN: 0143-3334 [Print] England
• PMID: 7127668 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Carcinogens
• Dimethylhydrazines
• Methylhydrazines
• DNA
• 1,2-Dimethylhydrazine

Topics

• 1,2-Dimethylhydrazine
• Animals
• Carcinogens
• Colon (metabolism)
• DNA (metabolism)
• Dimethylhydrazines (toxicity)
• Female
• Kidney (metabolism)
• Liver (metabolism)
• Male
• Methylation
• Methylhydrazines (toxicity)
• Rats
• Rats, Inbred Strains