This Article Full Text (PDF) References Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Add to Saved Citations Download to citation manager Add to My Marked Citations Citing Articles Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lubet, R. A. Articles by Diwan, B. A. Search for Related Content PubMed Articles by Lubet, R. A. Articles by Diwan, B. A. Social Bookmarking                         What's this?

Induction of Cytochrome P_450b and Its Relationship to Liver Tumor Promotion

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Building 538, Room 205E, Frederick, MD 21701–1013

R. W. Nims

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Building 538, Room 205E, Frederick, MD 21701–1013

J. M. Ward

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Building 538, Room 205E, Frederick, MD 21701–1013

J. M. Rice

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Building 538, Room 205E, Frederick, MD 21701–1013

B. A. Diwan

Laboratory of Comparative Carcinogenesis, Division of Cancer Etiology, National Cancer Institute-Frederick Cancer Research Facility, Building 538, Room 205E, Frederick, MD 21701–1013

A wide variety of compounds was examined for the ability to induce a specific form of hepatic cytochrome P₄₅₀ and to promote the development of DEN-initiated liver tumors (adenomas and carcinomas) in rats over a 72 week period. The induction of cytochrome P_450b was determined indirectly by measuring the hepatic induction of pentoxy-or benzyloxyresorufin O-dealkylase activities, which are highly specific substrates for the major phenobarbital-inducible forms of cytochrome P₄₅₀ in the rat.⁽¹⁰⁾ Results in the rat showed: (1) potent inducers (> 40 x) of P_450b (i.e., phenobarbital, barbital, ethylphenyl-hydantoin, and DDT) are all potent liver tumor promoters; (2) structural analogs that are not inducers of P_450b (i.e., hexobarbital, monoethylbarbituric acid, monophenyl-barbituric acid, and diethylhydantoin) all fail to display significant liver tumor promoting activity; and (3) the concomitant induction of liver hypertrophy, microsomal epoxide hydrolase, and cytochrome P_450b appears to be proportional and argues for some coordinated "pleiotropic" response of liver parenchyma to these inducers. Additional studies showed that phenobarbital induced cytochrome P_450b and was a liver tumor promoter not only in rats, but also in mice and patas monkeys, but was inactive as an enzyme inducer and was a nonpromoter in the hamster.

International Journal of Toxicology, Vol. 8, No. 2, 259-268 (1989)
DOI: 10.3109/10915818909019550


CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?