Study of Genotoxicity of Hepatocarcinogens in Multiple Organs in Mice by Feeding and Drinking Using the Comet Assay

Our study using the comet assay to detect genotoxicity of carcinogens in multiple mouse organs reveled that the correlation between genotoxicity and carcinogenicity on an organ-by-organ basis is not always high. One reason for this discrepancy is thought to be the difference in the administration method; carcinogenicity is detected by long-term administration at low doses, while genotoxicity has been detected by a single dose in the high dose range known as the maximum tolerated dose (MTD) using the comet assay. If there is such a large discrepancy between the results of in vivo genotoxicity and long-term carcinogenicity tests, it would be difficult to judge whether the experimentally suggested carcinogenicity is due to a genotoxic mechanism. Here, we compared the results of comet assay when carcinogens targeting and not targeting rodent liver were given by feeding or drinking with those when gavaged and examined the consistency with the results of carcinogenicity tests. Although single gavage of carcinogens targeting rodent liver at daily dose used in the carcinogenicity study induced DNA damage not only in the liver (carcinogenicity target organ) but also organs other than the liver, their triple gavages induced DNA damage only in the liver. Furthermore, their feeding and drinking for 4- and 6-days induced DNA damage in the carcinogenesis target organs. Their feeding and drinking for 1- and 2-days sometimes induced DNA damage in carcinogenesis not-targeting organs. Good correlation was shown between carcinogenicity targeting the liver and increase of their genotoxicity in the liver dependent to the duration of feeding and drinking period when they were given to mice continuously in the diet or drinking water. Therefore, the comet assay by continuous dosing of chemicals in the diet and drinking water would give useful information to predict carcinogenicity targeting sites.