Plasma alpha-fetoprotein elevation and mutagenicity of urine as early predictors of carcinogenecity in benzo(alpha)pyrene fed rats.
Weaning male Fischer rats were fed purified diets containing 0, 1, 100, or 1,000 ppm benzo(alpha)pyrene (BAP) for 6 weeks or 0, 1, or 100 ppm BAP for 3 weeks, then the same diets with or without 500 ppm sodium phenobarbital (PB) for an additional 5 weeks. Blood plasma alpha-fetoprotein (AFP) was determined at one to two week intervals. Urine, collected for eight hours during the sixth or eighth week of treatment, was tested for mutagenicity with S. typhimurium strain TA98 by the Salmonella/mammalian microsome test. Frozen liver sections were stained for gamma-glutamyl transpeptidase (GGT) activity. Only the 1000 ppm BAP treatment induced elevated blood plasma levels of AFP and GGT-positive hepatic cell foci. Urine from rats fed 1000 ppm BAP pr 100 ppm BAP + 500 ppm PB caused a significant (P less than or equal to .05) increase in revertants of S. typhimurium, compared to urine from control rats. Evidence from this investigation suggests that plasma AFP determination and urinary mutagenesis testing could be useful in short term in vivo screening for potential carcinogens.
D000818:Animals; D001564:Benzo(a)pyrene; D001580:Benzopyrenes / Q000633:toxicity*; D001835:Body Weight / Q000187:drug effects; D002273:Carcinogens; D008297:Male; D009153:Mutagens / Q000652:urine*; D009374:Neoplasms, Experimental / Q000378:metabolism; D010634:Phenobarbital / Q000494:pharmacology; D051381:Rats; D012486:Salmonella typhimurium / Q000235:genetics; D013997:Time Factors; D000509:alpha-Fetoproteins / Q000378:metabolism*; D005723:gamma-Glutamyltransferase / Q000378:metabolism
D001580:Benzopyrenes; D002273:Carcinogens; D009153:Mutagens; D000509:alpha-Fetoproteins; D001564:Benzo(a)pyrene; D005723:gamma-Glutamyltransferase; D010634:Phenobarbital