Increased smooth muscle cell proliferation by dimethylbenzanthracene is correlated to variations in activity of ornithine decarboxylase but not arylhydrocarbonhydroxylase.
Polycyclic aromatic hydrocarbons of cigarette smoke have been suggested to be involved in atherogenesis. After being converted to epoxides by monooxidases in the arterial wall the hydrocarbons may exert toxic or mutagenic effects on the smooth muscle cells (SMC). In a previous study we found that dimethylbenzanthracene (DMBA), an inducer of arylhydrocarbonhydroxylase (AHH), increased SMC proliferation and viability. In the present work we intended to study whether these effects were mediated by AHH. Alpha-naphtoflavone (ANF), a non specific AHH inhibitor, decreased SMC proliferation. The effects of ANF were totally counteracted by serum, partially by albumin and not at all by platelet derived growth factor. AHH activity was not detectable nor basally nor after induction in SMC, and this made us conclude that the effects of DMBA and ANF on SMC proliferation were not mediated by AHH. On the other hand the activity of ornithine decarboxylase was influenced by DMBA and ANF in parallel to proliferation, suggesting the involvement of this enzyme in the described DMBA effects on SMC proliferation. This mechanism might be of relevance for the pathogenesis of atherosclerosis especially in relation to cigarette smoking.
Department of Medicine, Malmö General Hospital, University of Lund, Sweden.
H
H
Pessah-Rasmussen
L
L
Stavenow
C B
CB
Xu
A
A
Berglund
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic; D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D009955:Ornithine Decarboxylase / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits
D015127:9,10-Dimethyl-1,2-benzanthracene; D001189:Aryl Hydrocarbon Hydroxylases; D009955:Ornithine Decarboxylase