Detection of mercapturic acids and nucleoside adducts in blood, urine and feces of rats treated with metabolites of methylpyrene

The carcinogen l-methylpyrene (MP) is metabolized via 1-hydroxymethylpyrene (HMP) to a sulfuric acid ester (SMP), which can covalently bind to nucleop hiles such as glutathione and DNA. These primary reaction products may be p rocessed to 1-methylpyrenyl mercapturic acid (MPMA) and free nucleoside add ucts [e.g. N-2-(1-methylpyrenyl)-deoxyguanosine, MPdG], and then be excrete d. MPMA may be considered as a marker for the amount of SMP which was detox ified, whereas MPdG represents that part which underwent uncontrolled react ions with tissue constituents. We have designed sensitive HPLC-MS/MS method s to determine levels of MPMA and MPdG in biological samples. Shortly after administration of HMP to rats, MPMA was detected in blood and was then exc reted in urine (> 70 %) and feces (< 30 %), chiefly within 24 h. The level of urinary MPMA was higher in females than in males. MPdG was detected in u rine of rat treated with SMP. Future investigations will focus on factors w hich modify the ratio of the excreted amounts of MPdG and MPMA in animals t reated with MP or its metabolites.