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)PI initiation and 12-O-tetradecanoylphorbol-13-acetate (TPA) promotion. SENCAR mice initiated with 101 ,ug/mouse B(a)P and promoted with TPA (2 ,g/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 jig/mouse, twice weekly) to B(a)P-initiated C57BL/6 mice (404 ,ug/mouse) for 50 weeks produced few papillomas. Substantial papilloma formation in C57BL/6 mice was observed after weekly treatment with B(a)P (101 jg/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 jig/mouse) papilloma formation after 30 weeks of TPA promotion (2 jig/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%k of the mice bore papillomas). The numbers of papillomas per mouse did not follow a Poisson distribution.These data can serve as a reference source for future comparisons of mouse skin tumor initiation results between SENCAR and other strains or stocks of mice and with other chemicals.

Role of Ultraviolet Radiation in Papillomavirus-Induced Disease

“…(2014) found that Cyclosporin A treatment is required for induction and maintenance of MmuPV1-induced papillomas in immunocompetent mice [ 18 ]. These authors did find that, at very high doses of virus (10 12 VGEs), the SENCAR strain of mice, selectively bred for high susceptibility to skin tumor induction by chemical carcinogens [ 44 ], developed papillomas, but these papillomas regressed within two weeks of appearing.…”

Rodent Papillomaviruses

“…If a very high dose of virus was used (1012 virus particles), papillomas did arise in C57/BL6 and SENCAR (SENsitivity to CARcinogenesis) strains of mice, but these papillomas regressed within one or two weeks post appearance [ 126 ]. Of these, the SENCAR strain of mice is a model that is classically used in skin tumorigenesis studies due to its high susceptibility to skin tumor induction by chemical carcinogens [ 127 , 128 ]. Continuous treatment with the immunosuppressant drug cyclosporine led to MmuPV1-induced papillomas in multiple immunocompetent mouse strains [ 120 , 126 ].…”

A responsive, sensitive, and reproducible dermal tumor promotion assay for the comparative evaluation of cigarette smoke condensates

“…The report concludes that SENCAR mice are the most acceptable strain for use in promotion studies (NTP, 1996), in agreement with an earlier Environmental Protection Agency (EPA) report (EPA, 1986). Nesnow et al (1986) reported the inter-experimental variability of papilloma formation from a series of 25 experiments with SENCAR mice after 30 weeks promotion with tetradecanoylphorbol. Low statistical variation was observed in papilloma multiplicity, papilloma incidence, or papilloma latency.…”