Excretion of an aflatoxin-guanine adduct in the urine of aflatoxin B1-treated rats.
Administration of aflatoxin B1 (AFB1) to rats resulted in the urinary excretion of 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1. This is the major product formed by the interaction in vivo of AFB1 with rat liver nucleic acids. The adduct was isolated from urine by the combined use of preparative and analytical high-pressure liquid chromatography and was quantitated by measurement of absorbance at 365 nm. The method allowed reproducible quantitation of adduct in urine samples from rats treated with AFB1 by i.p. injection at levels as low as 0.125 mg/kg. Application of the method to urine samples from rats given injections of AFB1 (1 mg/kg) revealed the presence of a compound chromatographically identical to authentic 2,3-dihydro-2-(N7-guanyl)-3-hydroxyaflatoxin B1. Spectral and chemical analysis of microgram quantities of this compound provided strong evidence that this compound is identical to authentic adduct. Measurement of this adduct in the urine of rats given injections of different doses of AFB1 showed that excretion occurs in a dose-dependent manner. Comparison of the dose-response curve for adduct excretion with that previously observed for adduct formation in rat liver DNA in vivo revealed a high degree of qualitative similarity, with the levels of adduct excreted in urine representing 30 to 40% of the levels seen initially in liver DNA.
D016604:Aflatoxin B1 / Q000031:analogs & derivatives; D000348:Aflatoxins / Q000378:metabolism* / Q000652:urine*; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004305:Dose-Response Relationship, Drug; D006147:Guanine / Q000031:analogs & derivatives* / Q000652:urine; D051381:Rats
D000348:Aflatoxins; D006147:Guanine; C028319:2,3-dihydro-2-(N(7)-guanyl)-3-hydroxyaflatoxin B1; D016604:Aflatoxin B1