DBA/2 mouse skin is unresponsive to dermal tumor promotion by cigarette smoke condensate

Previous studies demonstrated that repetitive application of cigarette smoke condensate (CSC) to 7,12-dimethylbenz[a]anthracene (DMBA)-initiated SENCAR mouse skin for 29 weeks at doses of 10, 20 and 40 mg “tar”/application results in time- and dose-dependent dermal tumor formation. To evaluate CSC-induced tumor promotion in other mouse skin models, male DBA/2 mice were treated with N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) (300 μg) or DMBA (75 or 150 μg) followed by promotion with 1R4F CSC at concentrations ranging from 9 to 45 mg “tar”/application. Both MNNG and DMBA have previously been shown to adequately initiate tumor development. Study end-points included clinical signs, body weights, and mass tracking. Neither the DMBA-initiated/acetone-promoted control groups, nor DMBA-initiated/CSC-promoted groups produced grossly observable skin tumors. For MNNG-initiated groups, a total of four tumors were observed. Based on these findings, it would appear the DBA/2 mouse was unresponsive to CSC dermal tumor promotion. It is not possible, based on the study design employed, to determine the underlying basis for the apparent resistance exhibited by this mouse strain to CSC-induced tumor promotion.