PROTECTIVE EFFECTS OF IN-VIVO 13-CIS-RETINOIC ACID TREATMENT AGAINST MUTAGEN-INDUCED GENETIC-DAMAGE

Our previous observation that 13-cis-retinoic acid (CRA) decreases mut agen induced genetic damage in vitro led us to the hypothesis that sim ilar protective effects are associated with in vivo CRA-treatment. The purpose of this study was to evaluate the changed in bleomycin-induce d chromatid breakage in peripheral blood lymphocytes over a course of treatment with CRA. The changes in bleomycin-induced chromatid breakag e were determined in serial blood samples obtained from 37 participant s of a chemoprevention trial. Subjects in this randomized double-blind trial received either 1 mg/kg/day CRA (per os) or placebo for 6 month s. The study evaluated the effects of CRA in reversing squamous metapl asia and/or dysplasia in biopsies of bronchial epithelium from chronic smokers. Four blood specimens were obtained during the study: at base line and after 1, 2, and 6 months of treatment. The changes in chromat id breakage over time in the CRA-treated group (n=20) were compared to those in the placebo-treated group (n=17) using repeated measures ana lysis of variance. Bleomycin-induced chromatid breakage decreased sign ificantly over time in the CRA-treated group (p<0.001) but not in the placebo group. Weak but statistically nonsignificant correlation was f ound between the decrease in chromatid breakage and elevation in serum CRA level among the CRA-treated subjects. Oral intake of CRA signific antly decreased bleomycin-induced genotoxicity in lymphocyte cultures from smokers with bronchial metaplasia. The antigenotoxic effect of CR A may be an important characteristic of this compound that may be util ized in the chemoprevention of upper aerodigestive tract cancers.