Human fibroblasts lacking trans-stilbene oxide active glutathione transferase exhibit increased cell death when exposed to polycyclic aromatic hydrocarbons.
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.
Pessah-Rasmussen
H
H
Department of Medicine, University of Lund, Malmö General Hospital, Sweden.
Stavenow
L
L
Seidegård
J
J
Berglund
A
A
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
D011083:Polycyclic Compounds; D013267:Stilbenes; D003094:Collagen; D004247:DNA; D005982:Glutathione Transferase; C025906:stilbene oxide