Urinary excretion of O6-butylguanine after the administration of N-nitroso-N-butylurea in rats.
O6-Butylguanine was detected in the urine of rats given the butylating agent N-nitroso-N-butylurea. O6-Butylguanine contents in the 24-h rat urine samples after i.p. doses of 50, 100, and 200 mg/kg N-nitroso-N-butylurea were 1.03 +/- 0.41 (SE), 8.30 +/- 1.70, and 59.53 +/- 6.52 pmol, respectively. This suggests that O6-butylguanine formation in nucleic acids might be repaired in vivo, possibly by base excision, besides other mechanisms. After i.v. doses of 0.1 and 1 mg/kg of O6-butylguanine to rats urinary excretion did not exceed 2% of the administered dose, suggesting that the amount of O6-butylguanine effectively released by base excision might be much larger than that detected in the urine after N-nitroso-N-butylurea. Inhibition of the enzyme O6-alkyl-DNA transferase by N-nitrosodimethylamine increased urinary O6-butylguanine resulting from exposure to N-nitroso-N-butylurea (100 mg/kg i.p.) up to four times, thus confirming an alternative DNA repair mechanism.
Airoldi
L
L
Laboratory of Environmental Pharmacology and Toxicology, Istituto di Richerche Farmacologiche Mario Negri, Milan, Italy.
Galli
A
A
Magagnotti
C
C
Bagnati
R
R
Lolli
M
M
Fanelli
R
R
D000818:Animals; D004247:DNA / Q000378:metabolism*; D004260:DNA Repair; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D008297:Male; D008780:Methyltransferases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016202:N-Methylaspartate / Q000494:pharmacology; D009607:Nitrosourea Compounds / Q000008:administration & dosage / Q000378:metabolism*; D019853:O(6)-Methylguanine-DNA Methyltransferase; D051381:Rats
D009607:Nitrosourea Compounds; D006147:Guanine; D016202:N-Methylaspartate; C046953:O(6)-n-butylguanine; C002738:N-nitrosobutylurea; D004247:DNA; D008780:Methyltransferases; D019853:O(6)-Methylguanine-DNA Methyltransferase