Journal of Toxicologic Pathology
Online ISSN : 1881-915X
Print ISSN : 0914-9198
ISSN-L : 0914-9198
Reviews
Biological Basis of Differential Susceptibility to Hepatocarcinogenesis among Mouse Strains
Robert R. Maronpot
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JOURNAL FREE ACCESS

2009 Volume 22 Issue 1 Pages 11-33

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Abstract

There is a vast amount of literature related to mouse liver tumorigenesis generated over the past 60 years, not all of which has been captured here. The studies reported in this literature have generally been state of the art at the time they were carried out. A PubMed search on the topic "mouse liver tumors" covering the past 10 years yields over 7000 scientific papers. This review address several important topics related to the unresolved controversy regarding the relevance of mouse liver tumor responses observed in cancer bioassays. The inherent mouse strain differential sensitivities to hepatocarcinogenesis largely parallel the strain susceptibility to chemically induced liver neoplasia. The effects of phenobarbital and halogenated hydrocarbons in mouse hepatocarcinogenesis have been summarized because of recurring interest and numerous publications on these topics. No single simple paradigm fully explains differential mouse strain responses, which can vary more than 50-fold among inbred strains. In addition to inherent genetics, modifying factors including cell cycle balance, enzyme induction, DNA methylation, oncogenes and suppressor genes, diet, and intercellular communication influence susceptibility to spontaneous and induced mouse hepatocarcinogenesis. Comments are offered on the evaluation, interpretation, and relevance of mouse liver tumor responses in the context of cancer bioassays.

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© 2009 The Japanese Society of Toxicologic Pathology
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