Temporal dynamics of cortisol and dexamethasone prevention of benzo(a)pyrene-induced morphological transformation of Syrian hamster cells.

The temporal aspects of the anticarcinogenic action of cortisol were investigated by measurement of the frequency of carcinogen-induced morphological transformation of Syrian hamster embryo cells relative to treatment regimen. Treatment of hamster cells with 10(-5) to 10(-11) M cortisol, dexamethasone, corticosterone, 17 beta-estradiol, progesterone, or testosterone did not result in morphological transformation. However, cortisol or dexamethasone treatment beginning 48 hr before the carcinogen caused a dose-dependent reduction in the transformation frequency associated with benzo(a)pyrene [B(a)P] or ultraviolet irradiation treatment. The frequency of B(a)P transformation was reduced 54, 66, and 84% by 10(-11), 10(-10), and 10(-9) M cortisol, respectively, without altering colony formation efficiency. Dexamethasone was equipotent as cortisol as an inhibitor of B(s)P, N-methyl-N'-nitro-N-nitrosoguanidine, or ultraviolet irradiation-induced transformation. Sex steroids, non-steroid antiinflammatory compounds, and steroids without antiinflammatory activity also reduced the transformation frequency but only at concentrations that reduced colony formation. Cortisol inhibition of transformation increased as steroid exposure occurred closer (48, 24, and 8 hr) yet prior to B(a)P treatment. In contrast, if cortisol was added simultaneously with or up to 72 hr after B(a)P, the frequency of transformation was unaffected. Dexamethasone addition after B(a)P, however, reduced the transformation frequency. Thus, physiological concentrations of cortisol when present prior to carcinogen exposure can prevent carcinogen-induced morphological transformation. The ability of cortisol to inhibit ultraviolet irradiation-induced transformation indicates that the anticarcinogenic activity may be mediated by steroid-induced cellular changes which are independent to metabolic activation of the carcinogen.