Metabolite profile in milk of lactating rats after treatment with a carcinogen, N-2-fluorenylacetamide.
Metabolites were determined in milk and urine of lactating rats 4 to 5 hr after each of 3 to 6 ip injections of N-2-fluorenylacetamide (2-FAA) at 0.2 mmol/kg of body weight. Milk contained 2-FAA as the major free compound, variable amounts of N-2-fluorenamine (2-FA) and phenols (7- greater than 5- greater than 3-hydroxy-2-FAA) chiefly as glucuronides, and very small amounts of the glucuronide of N-hydroxy-2-FAA. Urine contained large amounts of the phenols and N-hydroxy-2-FAA as free and conjugated compounds, but in contrast to milk, only small amounts of 2-FAA and no 2-FA. Pretreatment of rats with beta-napthoflavone, an inducer of microsomal C- and N-hydroxylations of 2-FAA, increased the amounts of 3- and 5-hydroxy-2-FAA in milk and of 3-hydroxy-2-FAA in urine. However, the total amounts of the compounds excreted in 1 ml of milk or urine, i.e. 0.05 to 0.13% or 0.6% of the dose of 2-FAA, respectively, were similar in the uninduced and induced groups. Protein hydrolysates of milk of 2-FAA-treated rats and of milk interacted with 2-nitrosofluorene (2-NOF) in vitro both contained 2-FA and 9-oxo-2-FA. This suggested formation of 2-NOF in vivo possibly by peroxidative metabolism of N-OH-2-FAA. Since 2-NOF has been reported to form adducts with unsaturated lipids, the effect of treatment of lactating rats with 2-FAA on the fatty acid composition of milk lipids was examined.(ABSTRACT TRUNCATED AT 250 WORDS)
D015073:2-Acetylaminofluorene / Q000493:pharmacokinetics* / Q000652:urine; D000818:Animals; D001711:Biotransformation; D002273:Carcinogens / Q000493:pharmacokinetics*; D002851:Chromatography, High Pressure Liquid; D005227:Fatty Acids / Q000378:metabolism; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007774:Lactation; D050356:Lipid Metabolism; D008297:Male; D008892:Milk / Q000378:metabolism*; D009560:Niridazole / Q000494:pharmacology; D011247:Pregnancy; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000378:metabolism
D002273:Carcinogens; D005227:Fatty Acids; D014280:Triglycerides; D015073:2-Acetylaminofluorene; D009560:Niridazole