Hemizygous Tg.AC transgenic mouse as a potential alternative to the two-year mouse carcinogenicity bioassay: evaluation of husbandry and housing factors

Assessing the Potential Carcinogenic Activity of Magnetic Fields Using Animal Models

“…Tests ofmagneticfields using the mouse skin modeL Although the use of transgenic models of epidermal carcinogenesis in mice is increasing [e.g., Holden et al (39); recent reviews by Brown et al. (40) and Arbeit (41) (48,49) or positive (50) effects of MF exposure, and one abstract that also reported positive results (51).…”

The use of genetically modified mice in cancer risk assessment: Challenges and limitations

“…This was particularly notable in the benzene bioassays where, in contrast to expectations and published reports (Table 4), some investigators observed reduced responses or no response using the Trp53 +/− or the Tg.AC mice (Holden et al, 1998; Storer, 1998; van der Laan, 2000). In the Tg.AC mice, the difference was believed to be due, at least in part, to the use of hemizygous mice rather than mice homozygous for the transgene (Holden et al, 1998). However, other reports are not consistent with that explanation (Spalding et al, 1999).…”

p27 Kip1 (Cdkn1b)-Deficient Mice Are Susceptible to Chemical Carcinogenesis and May Be a Useful Model for Carcinogen Screening

“…The transgene is not expressed in nontumor-bearing skin, but appears to be induced in response to full thickness wounding (2), ultraviolet irradiation (72) or chemical exposure (16,63). Nonetheless, specific and consistent housing and husbandry practices can effectively prevent false positive papillomas albeit at some additional cost per mouse (26). Spontaneous skin papilloma incidence in untreated or negative control groups of singlehoused mice has been reported to be less than 4% (26,35,69).…”

“…Nonetheless, specific and consistent housing and husbandry practices can effectively prevent false positive papillomas albeit at some additional cost per mouse (26). Spontaneous skin papilloma incidence in untreated or negative control groups of singlehoused mice has been reported to be less than 4% (26,35,69). The utility of the Tg.AC mouse, however, may be restricted to topical application of suspect carcinogens as oral gavage of chloroform failed to activate the v-H-ras transgene in the liver of treated mice (11).…”