Genetic susceptibility to environmental toxicants: the interface between human and experimental studies in the development of new toxicological concepts.
The growing knowledge of the genetic polymorphisms of enzymes metabolising xenobiotics in humans and their connections with individual susceptibility towards toxicants has created new and important interfaces between human epidemiology and experimental toxicology. The results of molecular epidemiological studies may provide new hypotheses and concepts, which call for experimental verification, and experimental concepts may obtain further proof by molecular epidemiological studies. If applied diligently, these possibilities may be combined to lead to new strategies of human-oriented toxicological research. This overview will present some outstanding examples for such strategies taken from the practically very important field of occupational toxicology. The main focus is placed on the effects of enzyme polymorphisms of the xenobiotic metabolism in association with the induction of bladder cancer and renal cell cancer after exposure to occupational chemicals. Also, smoking and induction of head and neck squamous cell cancer are considered.
Thier
Ricarda
R
Institut für Arbeitsphysiologie an der Universität Dortmund (IfADo), Ardeystrasse 67, Germany. r.thier@mailbox.uq.edu.au
Golka
Klaus
K
Brüning
Thomas
T
Ko
Yon
Y
Bolt
Hermann M
HM
D000818:Animals; D002273:Carcinogens / Q000009:adverse effects* / Q000378:metabolism / Q000633:toxicity; D002292:Carcinoma, Renal Cell / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D004781:Environmental Exposure / Q000009:adverse effects*; D004785:Environmental Pollutants / Q000009:adverse effects* / Q000378:metabolism; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005982:Glutathione Transferase / Q000235:genetics / Q000378:metabolism; D006258:Head and Neck Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006801:Humans; D007680:Kidney Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D017720:Molecular Epidemiology / Q000379:methods; D016273:Occupational Exposure / Q000009:adverse effects; D018675:Toxicity Tests / Q000379:methods; D014116:Toxicology / Q000379:methods; D001749:Urinary Bladder Neoplasms / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D015262:Xenobiotics / Q000009:adverse effects / Q000378:metabolism / Q000633:toxicity
D002273:Carcinogens; D004785:Environmental Pollutants; D015262:Xenobiotics; D003577:Cytochrome P-450 Enzyme System; D005982:Glutathione Transferase