Excretion of methylated nucleic acid bases as an indicator of exposure to nitrosatable drugs.
Urinary excretion of 3-methyladenine (3-meA) may be a valuable monitor of exposure to methylating carcinogens. In rats, the compound is known to be liberated from DNA following its formation, is not metabolized and is excreted intact in the urine. Studies with rats administered d3-methylating agents [e.g., a mixture of d6-aminopyrine (d6-AP) and nitrite which liberates d3-N-nitrosodimethylamine (NDMA) intragastrically] have confirmed that d3-3-meA is excreted in a dose-related manner. Although low levels of 'background' 3-meA have been found in rat and human urine, these are about 1000-fold lower than those of 7-methylguanine (7-meG). Thus, despite the fact that 3-meA is known to be formed at 10% of the level of 7-MeG in DNA following exposure of rats to methylating agents, the low 'background' that we have observed indicates that urinary 3-meA should be a more sensitive indicator of methylation than 7-meG.
Shuker
D E
DE
MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, UK.
Bailey
E
E
Farmer
P B
PB
D000225:Adenine / Q000031:analogs & derivatives* / Q000652:urine; D000818:Animals; D005260:Female; D006147:Guanine / Q000031:analogs & derivatives / Q000652:urine; D008745:Methylation; D009603:Nitroso Compounds / Q000493:pharmacokinetics*; D009696:Nucleic Acids / Q000378:metabolism*; D051381:Rats
D009603:Nitroso Compounds; D009696:Nucleic Acids; C025946:3-methyladenine; D006147:Guanine; C008450:7-methylguanine; D000225:Adenine