Proliferative responses of quail aortic smooth muscle cells to benzo[a]pyrene: implications in PAH-induced atherogenesis.
Repeated exposure of avian and rodent species to benzo(a)pyrene (BaP) has been associated with the development of aortic lesions of atherosclerotic etiology. Because the occurrence of these lesions may involve alterations in the regulation of smooth muscle cell (SMC) growth, the present studies were conducted to evaluate the proliferative responses of quail aortic SMCs to BaP treatment in vivo and in vitro. Measurements of [3H]thymidine incorporation and cell growth were conducted in cultured aortic SMCs isolated from male Japanese quail treated with 10 mg/kg BaP or vehicle weekly for 10 weeks or in naive aortic SMCs exposed in vitro to BaP (0.003-30 microM). Inhibition of DNA synthesis was observed in primary and early passage cultures of aortic SMCs isolated from BaP-treated quail relative to controls. Continued propagation of these cultures yielded a population of BaP cells which proliferated at faster rates than controls. The proliferative phenotype induced by BaP was first observed after the tenth passage and preserved in all subsequent passages tested. In vitro growth of SMCs from BaP-treated animals was serum- and anchorage-dependent. A 24-h exposure of cycling SMC cultures to BaP (0.003-30 microM) was associated with a dose-dependent decrease in DNA synthesis and significant delay in the progression of SMCs through the cell cycle. A time-course study revealed that maximal inhibition of DNA synthesis occurred 10 h after addition of 3 microM BaP to cycling cultures of SMCs. As seen in SMCs isolated from BaP-treated quail, serial subculture of SMCs exposed to 0.3 microM BaP in vitro for 24 h yielded a fast-growing population of cells. In these cultures, expression of the proliferative phenotype was observed after the fifth passage. These data suggest that BaP induces the expression of a proliferative phenotype in aortic SMCs characterized by enhanced serum responsiveness. This phenotypic modulation may contribute to the initiation and/or progression of vascular lesions of atherosclerotic etiology induced by BaP.
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Department of Physiology and Pharmacology, College of Veterinary Medicine, Texas A & M University, College Station 77843.
Ramos
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D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000473:pathology; D001161:Arteriosclerosis / Q000139:chemically induced / Q000473:pathology; D001564:Benzo(a)pyrene / Q000633:toxicity*; D002478:Cells, Cultured; D003370:Coturnix; D004247:DNA / Q000032:analysis; D004305:Dose-Response Relationship, Drug; D007770:L-Lactate Dehydrogenase / Q000032:analysis; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000473:pathology; D011083:Polycyclic Compounds / Q000633:toxicity; D014316:Tritium
D011083:Polycyclic Compounds; D014316:Tritium; D001564:Benzo(a)pyrene; D004247:DNA; D007770:L-Lactate Dehydrogenase