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A 26-week carcinogenicity study of 2-amino-3-methylimidazo[4,5-f]quinoline in rasH2 mice
Miwa Okamura1, Mitsuyoshi Moto, Masako Muguruma
1Laboratory of Veterinary Pathology, Tokyo University of Agriculture and Technology, Fuchu City, Tokyo, Japan. mokamura@cc.tuat.ac.jp
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.
Insights
rasH2 mice show increased susceptibility to the carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). Short-term testing in these genetically modified mice can effectively detect IQ's carcinogenic potential, particularly in the forestomach.
Area of Science:
- Toxicology
- Genetics
- Carcinogenesis
Background:
- 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) is a heterocyclic amine found in cooked foods.
- Its carcinogenic potential requires further investigation in susceptible animal models.
- The rasH2 transgenic mouse model offers enhanced sensitivity to carcinogens.
Purpose of the Study:
- To evaluate the carcinogenic susceptibility of rasH2 mice to IQ.
- To determine if a short-term (26-week) study can detect IQ's carcinogenic effects.
- To compare the effects of IQ in rasH2 mice versus wild-type (non-Tg) littermates.
Main Methods:
- 7-week-old rasH2 and non-Tg mice (male and female) were fed diets containing 0 or 300 ppm IQ for 26 weeks.
- Microscopical and histopathological examinations of forestomach and liver tissues were performed.
- Incidence of proliferative lesions and altered foci were analyzed.
Main Results:
- rasH2 mice fed IQ exhibited frequent forestomach proliferative lesions (hyperplasias, papillomas, carcinomas).
- No significant forestomach lesions were observed in non-Tg mice, regardless of IQ exposure.
- Increased incidence of hepatocellular altered foci was noted in female rasH2 mice exposed to IQ.
Conclusions:
- rasH2 mice are susceptible to the carcinogenic effects of IQ.
- A 26-week carcinogenicity test in rasH2 mice can effectively detect IQ's carcinogenic potential.
- This model is suitable for short-term carcinogenicity assessments of IQ.
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