PROTECTIVE EFFECT OF ALL-TRANS-RETINOIC ACID AGAINST TUMOR PROMOTION AND PROGRESSION IN LOW-RISK AND HIGH-RISK PROTOCOLS OF MOUSE SKIN CHEMICAL CARCINOGENESIS

In this study, we assessed the protective effects of all trans retinoi c acid (RA) against skin tumor promotion and progression in three diff erent protocols of mouse skin multistage carcinogenesis. Under these p rotocols, where papillomas on the skin of SENCAR mice were induced for their low- and high-probability of conversion to malignant carcinomas , pre-application of RA (10 mu g/mouse/application) to that of tumor p romoter 12-O-tetradecanoyl-phorbol-13-acetate (TPA) or mezerein (MEZ) in 7,12-dimethylbenz(a)anthracene (DMBA)-initiated mouse skin resulted in a highly significant protection against skin tumor promotion. In t erms of tumor incidence, multiplicity and volume/mouse, at the termina tion of the experiment at 20 weeks, RA showed 35-80%, 67-83% and 70-98 % protection, respectively. While the effect of RA was profound in all the protocols, maximum affectivity was evident in high-risk papilloma induction protocol where DMBA was used as tumor initiator and one wee k later TPA was applied once a week for five weeks. In tumor progressi on studies, at 20 weeks of standard low- and high-risk protocols, when papilloma yield is stabilized, animals which did not receive RA in di fferent protocols were divided into two groups and topically treated t wice weekly either with acetone or RA (10 mu g). These treatments were continued for an additional 29 weeks. During these treatments, all su spected carcinoma formation was recorded and carcinomas were verified histologically at the termination of the experiment. In each case, RA showed remarkable protective effects against percentage of mice with c arcinomas (35-45% protection), number of carcinomas per mouse (50-63% protection) and the rate of malignant conversion (50-63% protection). The results of the present study clearly demonstrate that irrespective of the risk for skin carcinogenesis, RA is capable of affording prote ction against the induction of nonmalignant lesions and their subseque nt conversion to malignancy.