Polymorphism of glutathione S-transferases and susceptibility to acrylonitrile and dimethylsulfate in cases of intoxication.
In this paper, the difficulties of genetic screening of occupationally exposed subjects for the evaluation of retrospective, and prospective, health risk assessments is illustrated with reference to glutathione S-transferase (GST) function. Individual differences in the magnitude and half-life of adduct levels, derived from background and occupational exposure, are observed largely independently of genetically determined conjugator status. During detoxification, GSTs play a critical role in providing protection against electrophiles and products of oxidative stress. GSTs are a superfamily of enzymes that may have broad and overlapping substrate specificities. Deficiencies of GST isoenzymes may be compensated by the presence of other isoforms and by the use of alternative metabolic pathways. This may be one reason for the abundance of controversial data on GST polymorphisms and adverse health effects.
Bayer AG Leverkusen, Medical Service, Building L 9, D-51368 Leverkusen, Germany.
Gabriele
G
Leng
Jürgen
J
Lewalter
D000181:Acrylonitrile / Q000493:pharmacokinetics / Q000506:poisoning*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005858:Germany; D005914:Globins / Q000378:metabolism; D005982:Glutathione Transferase / Q000172:deficiency / Q000235:genetics*; D006801:Humans; D006856:Hydrogen Cyanide / Q000097:blood; D007073:Immunoglobulin E / Q000032:analysis; D008658:Inactivation, Metabolic; D008297:Male; D011110:Polymorphism, Genetic; D012907:Smoking; D013463:Sulfuric Acid Esters / Q000493:pharmacokinetics / Q000506:poisoning*
D013463:Sulfuric Acid Esters; D006856:Hydrogen Cyanide; D007073:Immunoglobulin E; D005914:Globins; D005982:Glutathione Transferase; C007482:dimethyl sulfate; D000181:Acrylonitrile