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 Similar articles in PubMed Alert me to new issues of the journal Add to Saved Citations Download to citation manager Request Permissions Request Reprints Add to My Marked Citations Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Citing Articles via Scopus Google Scholar Articles by Lewis, D. F. Articles by Parke, D. V Search for Related Content PubMed PubMed Citation Articles by Lewis, D. F. Articles by Parke, D. V Social Bookmarking                         What's this?

A combined COMPACT and HazardExpert study of 40 chemicals for which information on mutagenicity and carcinogenicity is known, including the results of human epidemiological studies

Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, Surrey GU2 5XH, UK

Costas Ioannides

Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, Surrey GU2 5XH, UK

Dennis V Parke

Molecular Toxicology Group, School of Biological Sciences, University of Surrey, Guildford, Surrey GU2 5XH, UK

The COMPACT approach for defining structural criteria for substrates and inducers of cytochrome P450 (CYP) enzymes which mediate the formation of reactive intermediates is discussed in the context of prediction of potential carcinogenicity. This is broadened to encompass structural studies on mammalian P450s, including those relevant to genetic polymorphism in man. The use of the COMPACT system, in parallel with the structure alert program HazardExpert (now incorporated into the Pallas system), for evaluating human carcinogenicity data is reported, as an example of the possible employment of a battery of short-term test procedures for safety evaluation. In particular, the importance of using the log P value (as a measure of compound lipophilicity) to assess the likelihood of a potentially toxic compound reaching the site of activation, is emphasized by the finding that most procarcinogens requiring metabolic activation by P450s are lipophilic in nature.

Key Words: COMPACT • cytochrome P450 • HazardExpert • carcinogenicity • evaluation

Human & Experimental Toxicology, Vol. 17, No. 10, 577-586 (1998)
DOI: 10.1177/096032719801701009


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

This article has been cited by other articles:

				D F. Lewis, M G Bird, and M N Jacobs Human carcinogens: an evaluation study via the COMPACT and HazardExpert procedures Human and Experimental Toxicology, March 1, 2002; 21(3): 115 - 122. [Abstract] [PDF]