Activation of dihaloalkanes by thiol-dependent mechanisms.
Dihaloalkanes constitute an important group of chemicals because of their widespread use in industry and agriculture and their potential for causing toxicity and cancer. Chronic toxic effects are considered to depend upon bioactivation, either by oxidation or thiol conjugation. Considerable evidence links genotoxicity and cancer with glutathione conjugations reactions, and some aspects of the mechanisms have been clarified with 1,2-dihaloalkanes and dihalomethanes. Recently the DNA repair protein O6-alkylguanine transferase has been shown to produce cytotoxicity and genotoxicity by means of a thiol-dependent process with similarities to the glutathione reactions.
Guengerich
F Peter
FP
Department of Biochemistry and Center in Molecular Toxicology, Vanderbilt University School of Medicine, Nashville, TN 37232-0146, USA. guengerich@toxicology.mc.vanderbilt.edu
D018736:DNA Adducts / Q000737:chemistry / Q000378:metabolism*; D015946:Ethylene Dibromide / Q000378:metabolism / Q000633:toxicity; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D006846:Hydrocarbons, Halogenated / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity*; D008658:Inactivation, Metabolic; D019853:O(6)-Methylguanine-DNA Methyltransferase / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000378:metabolism*
D018736:DNA Adducts; D006846:Hydrocarbons, Halogenated; D013438:Sulfhydryl Compounds; D015946:Ethylene Dibromide; D019853:O(6)-Methylguanine-DNA Methyltransferase; D005978:Glutathione