PAPILLOMAS AT HIGH-RISK FOR MALIGNANT PROGRESSION ARISING BOTH EARLY AND LATE DURING 2-STAGE CARCINOGENESIS IN SENCAR MICE

The current study was designed to further establish that most papillom as produced in SENCAR mice during two-stage skin carcinogenesis are, i n fact, premalignant lesions and to specifically determine the maligna nt conversion potential of papillomas that arise at different times du ring the carcinogenesis process, A method was established to physicall y map and monitor the lifespan of all papillomas produced in SENCAR mi ce during the course of an initiation-promotion experiment using DMBA as the initiator and 12-O-tetradecanoylphorbol-13-acetate (TPA) as the promoter. The results from these experiments showed that in groups of mice initiated with either 0.5 or 2.0 mu g DMBA, long-term (60 weeks) treatment with TPA yielded a significantly higher number of SCCs comp ared to shortterm treatment (7 weeks). Papillomas that emerged after 1 1 weeks and thereafter in all treatment groups had the ability to prog ress to SCCs, The median conversion time for all papillomas in all gro ups was 26 weeks. When corrected for median conversion time, papilloma s that emerged in week II and thereafter in all treatment groups had s imilar or greater conversion ratios compared to those that emerged wit hin the first 10 weeks. Interestingly, the median conversion time was significantly shorter (18 versus 27 weeks, respectively; P<0,0002) for papillomas that emerged in week 11 and thereafter compared to those t hat emerged at or prior to 10 weeks for all groups. The data in this s tudy demonstrate that papillomas arising throughout a two-stage carcin ogenesis protocol in SENCAR mice progress to SCCs, Many papillomas tha t arise later in two-stage carcinogenesis protocols do not have suffic ient time to allow for conversion and should be excluded from the anal yses. Furthermore, another novel finding of the current study was the observation that papillomas arising later in the two-stage protocol (> 11 weeks) progressed to SCCs at a faster rate than those that arose ea rliest in the protocol.