Investigation on optimal conditions of 5 α-reductase inhibitor in prevention of prostate carcinogenesis

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We examined whether a 5 α-reductase inhibitor, FK143, does or does not suppress prostate carcinogenesis in spontaneously cancer-developing rat model, ACI/Seg rats. The rats were fed on diet containing FK143 at 20ppm or 200ppm from 80 weeks to 140 weeks of age, or at 20ppm from 6 weeks, 40 weeks and 60 weeks to 100 weeks of age. At the end of treatment, the rats were sacrificed for histological examinations and tissue androgen assay for the ventral prostate. Carcinogenesis was inhibited only in that incidence of macroscopic cancer was significantly less frequent in those fed 20ppm of FK143 from 80 weeks to 140 weeks. In any other groups the incidence of atypical hyperplasia, microscopic cancer or macroscopic cancer was comparable or even increased compared with the control. Androgen assay showed significant suppression of dihydrotestosterone concentration in any treated groups. However testosterone concentration was unaffected only in the group in which carcinogenesis was suppressed ; it was reciprocally increased in other groups in which carcinogenesis was NOT suppressed. Taken together, FK143 inhibits 5 α-reductase activity in the rat prostate and may suppress carcinogenesis provided it does not accumulate the substrate, testosterone, in the prostate.