title: Human fibroblasts lacking trans-stilbene oxide active glutathione transferase exhibit increased cell death when exposed to polycyclic aromatic hydrocarbons.
abstract: Glutathione transferases (GST) are detoxifying enzymes who act with many endogenous and exogenous substances such as polycyclic aromatic hydrocarbons (PAH). The GST activity towards trans-stilbene oxide (GST-tSBO) is inherited in an autosomal dominant fashion and can be separated in high (GST-positive) and low (GST-negative) phenotypes when measured in blood. Human fibroblast cultures were established from males matched for age, smoking habits and clinical manifestations of atherosclerosis. Matched pairs of GST-negative and GST-positive fibroblasts were studied. There was a very strong correlation between the levels of GST-tSBO in peripheral blood and in cultured fibroblasts within the same individual. When fibroblasts were exposed to benzo(a)pyrene (BP) or dimethylbenzanthracene (DMBA) GST-negative cells produced relatively more collagen than GST-positive cells. GST-negative fibroblasts showed a greater cell death than GST-positive fibroblasts as well among controls as after exposure to PAH. It is concluded that lack of GST-tSBO is easily discriminated in cultured skin fibroblasts. GST-negative and GST-positive fibroblasts showed different susceptibility towards some toxic stimuli that might be of importance in atherogenesis.
authors.affiliation: Department of Medicine, University of Lund, Malmö General Hospital, Sweden.
authors.forename: H
authors.initials: H
authors.lastname: Pessah-Rasmussen
authors.forename: L
authors.initials: L
authors.lastname: Stavenow
authors.forename: J
authors.initials: J
authors.lastname: Seidegård
authors.forename: A
authors.initials: A
authors.lastname: Berglund
mesh_terms: D000368:Aged; D016923:Cell Death / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D005347:Fibroblasts / Q000187:drug effects* / Q000201:enzymology*; D005982:Glutathione Transferase / Q000032:analysis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D011083:Polycyclic Compounds / Q000494:pharmacology*; D012867:Skin / Q000166:cytology; D013267:Stilbenes
chemical_list: D011083:Polycyclic Compounds; D013267:Stilbenes; D003094:Collagen; D004247:DNA; D005982:Glutathione Transferase; C025906:stilbene oxide