Carcinogenic Effect of N-Nitrosodimethylamine on Diploid and Triploid Zebrafish (Danio rerio)

Abstract

Viability of polyploid organisms in lower vertebrates including fish provides an additional tool to investigate genetic mechanisms of neoplastic transformation caused by carcinogens. Here we present data on differential sensitivity of diploid and triploid zebrafish ( Danio rerio) to N-nitrosodimethylamine (NDMA) induced hepatocarcinogenesis. The effect of the carcinogen was studied in 100 diploid and 120 triploid zebrafish. Zebrafish, age 5—6 weeks, were exposed to 50 ppm NDMA for 8 weeks and then were transferred into fresh carcinogen-free water until necropsy. At the necropsy performed 24 weeks after beginning the treatment, cholangiolar tumors (cholangiocarcinomas and cholangiomas) were essentially observed in diploid zebrafish only, while the incidence of hepatocellular tumors (hepatocellular carcinomas and adenomas) was similar in diploid and triploid zebrafish, 7.7% and 9.5%, respectively. By contrast, 36 weeks after beginning the treatment, the incidence of hepatocellular tumors was significantly lower in diploid animals as compared to triploid ones, 10.3% and 33.8%, respectively. The incidence of cholangiolar tumors in diploid and triploid zebrafish was not significantly different, 10.3% and 14.9%, respectively. Therefore, the increase of ploidy appeared to have a differential effect on the induction of these 2 types of liver tumors in zebrafish. This finding suggests a difference in genetic mechanisms of the tumor development revealed by utilization of triploid animals in this study. However, triploid zebrafish demonstrated an overall increase in latency period in the development of both types of hepatic tumors, a finding that can be interpreted as an increased resistance of triploid animals to the carcinogenic effect of NDMA.