Development and initial characterization of several new inbred strains of SENCAR mice for studies of multistage skin carcinogenesis

The development and initial characterization of five new inbred strains of SENCAR mice are described in this paper. Ten randomly selected pairs of out bred SENCAR mice mere mated and offspring from each separately maintained p arental line were sib mated at each successive generation to result in inbr ed strains. Due to poor reproductive performance only five of the original 10 lines mere bred to homogeneity, Initial characterization of the five rem aining lines (referred to as SL2/sprd, SL5/sprd, SL7/sprd, SL8/sprd and SL1 0/sprd) at F12 for their responsiveness to a two-stage carcinogenesis proto col (10 nmol 7,12-dimethylbenz[a]anthracene and 0.25 mu g 12-O-tetradecanoy lphorbol-13 acetate) revealed three groups of responders in terms of the nu mber of papillomas per mouse: SL2/sprd and SL8/sprd > SL7/sprd and SL10/spr d >> SL5/sprd, The papilloma responses in SL2/sprd and SL8/sprd were very s imilar to SENCAR B/Pt compared at the same doses, Papillomas induced on SL2 /sprd had the highest propensity to progress to squamous cell carcinomas, s imilar to that observed in outbred SENCAR and SENCAR B/Pt mice. More detail ed comparison of the responsiveness of SL2/sprd and SL5/sprd at F15 showed that these two inbred strains differed in their sensitivity to TPA-induced epidermal hyperplasia and that the dose of TPA required to produce a tumor response in SL5/sprd in comparison with that in SL2/sprd was 4-20 times hig her. Overall, the availability of the different inbred SENCAR strains will greatly aid mechanistic studies of multistage skin carcinogenesis as well a s studies to understand the underlying genetic basis of resistance to tumor promotion and progression in this model system.