Limited Effects of Disrupted Gap Junctions in the Liver on Multi-organ Carcinogenesis Induced by Diisopropanolnitrosamine in the Mutant Connexin 32 Transgenic Rat

Gap junctions, composed from molecules called connexins, play important roles in cell-to-cell communication and aberrant gap junctional intercellular communication (GJIC) has been reported in many types of cancers. We have established transgenic rats bearing a dominant negative mutant of the connexin 32 gene under control of the albumin promoter. In these rats, GJIC is markedly decreased in the liver, and is associated with increased induction of preneoplastic foci after a single treatment of diethylnitrosamine. In the present study, in order to explore whether organs other than the liver would demonstrate increased susceptibility to a carcinogen, we treated these transgenic rats (having disrupted GJIC of the liver) with diisopropanolnitrosamine (DHPN), a carcinogen targeting multiple organs, such as the liver, lung, kidney and thyroid gland. We found that increased susceptibility for the carcinogenicity was evident only in the liver, but not in the lung, kidney and thyroid gland. This result indicates that disrupted GJIC in the liver influences the liver carcinogenesis, but has no effect on carcinogenesis in other organs.