Comparison of the tumorigenic response of SENCAR and C57BL/6 mice to benzo(a)pyrene and the inter-experimental variability over a three-year period.

Abstract

SENCAR and C57BL/6 mice were compared for their ability to produce tumors after benzo(a)pyrene [B(a)P] initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. SENCAR mice initiated with 101 micrograms/mouse B(a)P and promoted with TPA (2 micrograms/mouse, twice weekly) produced large numbers of papillomas, whereas C57BL/6 mice produced none after 26 weeks of promotion. Continued treatment of the B(a)P-initiated C57BL/6 mice with TPA up to 52 weeks did not induce any papillomas nor did higher doses of B(a)P. Application of increased doses of TPA (10 micrograms/mouse, twice weekly) to B(a)P-initiated C57BL/6 mice (404 micrograms/mouse) for 50 weeks produced few papillomas. Substantial papilloma formation in C57BL/6 mice was observed after weekly treatment with B(a)P (101 micrograms/mouse), with maximal production occurring at weeks 39 to 41 of treatment. In contrast, SENCAR mice treated according to the same protocol produced an equivalent response with maximal papilloma formation occurring 12 to 13 weeks earlier. Therefore, C57BL/6 mice exposed to B(a)P are capable of producing papillomas under certain experimental conditions. The inter-experimental variability of B(a)P-induced (50.5 micrograms/mouse) papilloma formation after 30 weeks of TPA promotion (2 micrograms/mouse, twice weekly) was examined in SENCAR mice over a 37-month period. Low statistical variation was observed in papilloma multiplicity, papilloma incidence, or papilloma latency. Male and female SENCAR mice produced equal values in the three parameters: 4.4 +/- 1.6 papillomas/mouse, 87% +/- 10% of the mice bearing papillomas, and 9.6 +/- 1.3 weeks (time at which 10% of the mice bore papillomas). The numbers of papillomas per mouse did not follow a Poisson distribution.(ABSTRACT TRUNCATED AT 250 WORDS)