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Phenobarbital Does Not Promote Hepatic Tumorigenesis in a Twenty-Six-Week Bioassay in p53 Heterozygous MiceProduct Safety Assessment, Searle, St. Louis, Missouri 63167
Product Safety Assessment, Searle, St. Louis, Missouri 63167
Product Safety Assessment, Searle, St. Louis, Missouri 63167
Product Safety Assessment, Searle, St. Louis, Missouri 63167
Product Safety Assessment, Searle, St. Louis, Missouri 63167
Product Safety Assessment, Searle, St. Louis, Missouri 63167 The tumorigenic potential of phenobarbital was examined in a 26-wk carcinogenesis bioassay using p53 heterozygous mice and wild-type controls. Fifteen mice/sex/genotype were exposed to either 500 or 1,000 ppm phenobarbital in the diet. Dietary administration of 3,750 ppm p-cresidine, a transspecies mutagenic carcinogen, to both heterozygous and wild-type mice served as a positive control. Phenobarbital treatment caused increases in liver: body weight ratios and histologic evidence of centrilobular hepatocellular hypertrophy. No tumors were observed in any phenobarbital-treated mice. Mice given p-cresidine exhibited a moderate reduction in body weight gain over the couise of the study. Heterozygous mice treated with p-cresidine exhibited a high incidence of urinary bladder tumors. Similar tumors were also present in a small number of p-cresidine-treated wild-type mice. Our results demonstrate the lack of a hepatic tumor response to phenobarbital, a compound that is a potent and prototypic hepatic microsomal enzyme inducer, a nongenotoxic rodent carcinogen, and a human noncarcinogen. This finding supports the continued utility of this model as an alternative to the mouse bioassay for human carcinogenic safety assessment of potentially genotoxic carcinogens because it did not produce a false-positive response to this potent nongenotoxic agent.
Key Words: p-Cresidine • urinary bladder • liver • carcinogenesis • bioassay • neoplasia
Toxicologic Pathology, Vol. 26, No. 4,
492-500 (1998) This article has been cited by other articles:
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