Combinations of Susceptible Genotypes and Individual Responses to Toxicants
Ari Hirvonen
Finnish Institute of Occupational Health, Helsinki, Finland
Abstract
The variation in individual responses to exogenous agents has been shown to be exceptionally wide. It is because of this large diversity of responsiveness that risk factors to environmentally induced diseases have been difficult to pinpoint, particularly at low exposure levels. Opportunities now exist for studies of host factors in environmentally induced cancer or other diseases in which an environmental component can be presumed. Many of the studies have shown an elevated disease proneness for individuals carrying the potential at-risk alleles of metabolic genes, but a number of controversial results have also been reported. One possible explanation for the divergent findings is lack of knowledge of the other potentially relevant genotypes for a given exposure. This paper gives an overview of the published data on combinations of metabolic genotypes in relation to individual susceptibility to environmental toxicants. --Environ Health Perspect 105(Suppl 4):755-758 (1997)
Key words: CYP1A1, CYP2E1, CYP2D6, GSTM1, GSTT1, NAT1, NAT2, genetic polymorphisms
This paper was prepared as background for the Workshop on Susceptibility to Environmental Hazards convened by the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC) held 17-22 March 1996 in Espoo, Finland. Manuscript received at EHP 5 November 1996; accepted 18 November 1996.
Address correspondence to Dr. A. Hirvonen, Finnish Institute of Occupational Health. Department of Industrial Hygiene and Toxicology, Topeliuksenkatu 41 a A, FIN-00250 Helsinki, Finland. Telephone: 358-9-4747204. Fax: 358-4747208. E-mail: ari.hirvonen@occuphealth.fi
Abbreviations used: CYP, cytochrome P450; GST, glutathione S-transferase; NAT, N-acetyltransferase; PCR, polymerase chain reaction.
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