Modulations of TCDD-mediated induction of zebrafish cyp1a1 and the AHR pathway by administering Cd 2+ in vivo.

Trace metal ions such as cadmium (Cd2+ ) and trace organics typified by 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) are common co-contaminants in the environment and cause toxic effects in aquatic organisms that pose serious health risks. We studied the effects of Cd2+ on the regulation of cytochrome P450 1A1 (cyp1a1) gene-induction by TCDD using zebrafish embryos and larvae and adult zebrafish tissues. Our results showed that TCDD induced the cyp1a1 gene in all developmental stages and tissues of zebrafish, and the induction was higher in females than males. However, for the upstream genes (ahr2 and arnt2b) that mediate cyp1a1 gene induction in the zebrafish liver cell line was not induced by TCDD similar to the pattern of cyp1a1 in all investigated groups. After co-treatment with Cd2+ , induction of the aryl hydrocarbon receptor pathway by TCDD was inhibited in the zebrafish larvae and the livers, intestines, kidneys and gills of adult zebrafish, but not in the embryos or brains of adult zebrafish, indicating that the toxicological effects of Cd2+ on TCDD are dependent on the developmental stages and tissue types. The present study confirms that Cd2+ blocks the TCDD-induced cyp1a1 gene in vivo but emphasizes that the effects are specific to the developmental stage, type of tissue and sex. The combined effects of Cd2+ and TCDD must be taken into consideration together with these parameters to accurately predict and assess cadmium and TCDD-induced toxicity in fish and carcinogenesis in animals in general.