Further studies on the influence of initiation dose on papilloma growth and progression during two-stage carcinogenesis in SENCAR mice

The present study was designed to further evaluate the growthand progression of papillomas to squamous cell carcinomas (SCCs)in groups of animals receiving initiating doses of 7,12-dimethylbenz[a]anthracene(DMBA) producing relatively low papilloma yields following longterm promotion (60 weeks) with 12-O-tetradecanoylphorbol-13-acetate(TPA). For comparison, groups of animals were initiated withvarious doses of DMBA and then promoted with mezerein (MEZ),benzoyl peroxide (BzPo) and chrysarobin (CHRY). Following initiation,groups of female SENCAR mice received the following promoterdoses: TPA (1.0 or 2.0 µg per mouse); MEZ (2.0 µgper mouse); BzPo (20.0 mg per mouse); and CHRY (52.8 µgper mouse). The maximum papilloma to SCC conversion ratio obtainedwith TPA in the current study was 0.32. This value was in therange of maximum conversion ratios obtained with the other compounds:MEZ, 0.40; CHRY, 0.32 and BzPo, 0.19. In general, the highestpapilloma to SCC conversion ratios observed with TPA as thepromoter were obtained in groups that received the lowest dosesof DMBA and had relatively low papilloma burdens. A comparisonof papilloma to SCC conversion in groups of mice promoted withTPA, MEZ or CHRY and having similar papilloma yields, revealedvery similar conversion ratios. Comparison of the BzPo groupwith a similar papilloma yield indicated that the conversionratio was slightly lower with this promoter. The present resultsindicate that in mice promoted with TPA and having relativelylow papilloma numbers, a larger proportion of these papillomasprogress to SCCs during continued promoter treatment. Furthermore,the results suggest that papillomas behave similarly in theirability to progress to SCCs regardless of the promoter usedwhen comparing groups of mice with similar tumor numbers. Thedata are discussed in terms of possible mechanisms for the observedresults.