The effects of retinoic acid on the expression of the Ha-ras gene were studied in transformed rat hepatoma cells (H4IIE) and in rat aortic smooth muscle cells (ASMC) treated with benzo(a)pyrene (30 microM) in vitro. In H4IIE cells, a dose-dependent increase in steady state Ha-ras mRNA levels was observed upon exposure to retinoic acid for 24 hr. Exposure of ASMC to 10 microM retinoic acid under similar experimental conditions was also associated with increased Ha-ras expression. In contrast, retinoic acid (1 and 10 microM) inhibited benzo(a)pyrene-induced expression of Ha-ras in ASMC. These results suggest that retinoic acid modulates spontaneous and carcinogen-induced expression of Ha-ras in a differential manner.
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