Abstract
Benzo(a)pyrene (BaP) elicits a diverse spectrum of toxic and biochemical responses in different species, i.e. cytotoxicity, immunotoxicity, mutagenicity, carcinogenicity, and atherogenicity. Previous studies have been shown that repeated exposure rodent and avian species to BaP in vivo resulted in atherosclerotic lesions involving alterations in vascular smooth muscle cell (SMC) proliferation. The present studies were conducted to study the mechanism of BaP-induced deregulation of SMC proliferation. 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. Inhibition of C-kinase mediated phosphorylation of endogenous Mr 272, 72, and 45 kDa proteins was observed in the particulate fraction of aortic homogenates from BaP-treated quail relative to controls. PKC activity in the particulate, but not cytosolic fraction, was decreased by BaP treatment. Inhibition of BaP on c-fos expression was seen as early as 30 min, but became most pronounced at 1 hr. Inhibition of AP1 binding ability was observed when growth-arrested SMCs were exposed to 30 uM BaP for 2, 5, and 24 hr in the presence of serum. BaP inhibited c-myc gene expression at 1 hr, but increased myc expression by 2 hr following challenge with serum. BaP increased ras expression at 16 hr after growth-arrested SMCs were treated with BaP in the presence of serum. When growth-arrested cells were treated with 30 uM BaP for 24 hr in the presence of serum followed by maintenance under regular culture conditions for up to 130 days, BaP-treated cells expressed a proliferative phenotype characterized by increased DNA synthesis, c-fos expression, AP1 binding ability, and c-myc expression.
Ou, Xiaolan (1994). Modulation of vascular smooth muscle cell proliferation by Benzo(A)pyrene : mechanistic studies. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -1551987.