A 26-Week Carcinogenicity Study of 2-Amino-3-Methylimidazo[4,5-f]Quinoline in rasH2 Mice

Abstract

To evaluate the carcinogenic susceptibility of rasH2 mice to 2-amino-3-methylimidazo[4,5-f ]quinoline (IQ), 7-week-old rasH2 mice and their wild-type littermates (non-Tg mice) of both the sexes were fed a diet containing 0 or 300 ppm IQ for 26 weeks. Microscopical examinations revealed that the proliferative lesions of the forestomach, including squamous cell hyperplasias, papillomas, and carcinomas, were frequently encountered in male and female rasH2 mice fed with IQ. In non-Tg mice, no significant differences in the incidence of forestomach lesions were observed between the 0 ppm and 300 ppm groups. Histopathological changes such as periportal hepatocellular hypertrophy and oval cell proliferation in the liver were more apparent in female rasH2 and non-Tg mice than in males, and the incidence of hepatocellular altered foci significantly increased in female rasH2 mice in the 300 ppm group as compared to that in the 0 ppm group. These results suggest that the carcinogenic potential of IQ can be detected in rasH2 mice by a 26-week, short-term carcinogenicity test.

Spontaneous Tumor Incidence in rasH2 Mice

“…To compare the internally generated tumor incidence data with previous reports in rasH2 mice, tumor incidence from control and MNU-treated rasH2 mice from 6-month carcinogenicity studies were also collated from literature published from 2001-2011 (Table 2) (Cho et al 2010;Jin et al 2007;Machida et al 2008;Okamura et al 2006Okamura et al , 2007Palazzi and Kergozien-Framery 2009;Usui et al 2001). It is important to note that MNUrelated tumor incidences in the Pfizer studies were obtained from study reports and not by retrospective analysis of slides.…”