Despite widening interest in the possible association between
infection/
inflammation and
cancer development, knowledge of this issue in relation to
oral cancer remains inadequate. This study aimed to determine the susceptibility of Apc-mutant Kyoto Apc Delta (KAD) rats, which are vulnerable to developing
inflammation-associated colorectal
carcinogenesis, to 4-nitroquinoline 1-oxide (4-NQO)-induced tongue
carcinogenesis in order to clarify the role of
inflammation in
oral cancer. KAD (20 males and 22 females) and F344/NS1c (22 males and 23 females) rats received
drinking water with or without 4-NQO (20 ppm) for eight weeks. Histopathological and immunohistochemical analyses of the tongue were performed at week 20. Additionally, the
mRNA expression of inflammatory
cytokines in the tongue mucosa was determined at week 8. Tongue
squamous cell carcinoma (SCC) developed in the KAD and F344/NS1c rats that received 4-NQO. Regardless of gender, the incidence and multiplicity of tongue SCC were greater in the KAD rats than in the F344/NS1c rats. In addition, the multiplicity of tongue SCC in the female KAD rats was significantly greater than that observed in the male KAD (p < 0.01) and female F344/NS1c rats (p < 0.05). The levels of
inflammation and the
mRNA expression of inflammatory
cytokines in the tongue in the 4-NQO-treated female KAD rats were the highest among the rats given 4-NQO. These results show that KAD rats, particularly females, are susceptible to 4-NQO-induced tongue
carcinogenesis, suggesting the utility of models employing KAD rats for investigating the pathobiology of oral (tongue)
carcinogenesis associated with
inflammation.