Relating genotoxicity to DNA repair and reproductive success in zebrafish (Danio rerio) exposed to environmental toxicants

Abstract

The potential for environmental toxicants to cause genetic damage (genotoxicity) in organisms is a prominent concern because effects on DNA can compromise reproductive success and survival in organisms. Genotoxicity in male germ cells is of particular concern because damage to DNA in sperm may not be repaired and the consequences of damaged genetic material may be transgenerational (from parent to offspring). An integrated approach across multiple levels of biological organization is necessary to establish linkages between exposure to genotoxicants and subsequent effects at molecular and higher levels of biological organization. This thesis addresses the relation between toxicant-induced genotoxicity and reproductive success in zebrafish, and focuses on a model genotoxicant (hydrogen peroxide) and dissolved metals (radionuclide or non-radioactive forms) under controlled laboratory conditions. Uptake and depuration kinetics of a mixture of radionuclides (54Mn, 60Co, 65Zn, 75Se, 109Cd, 110mAg, 134Cs, and 241Am) were investigated, and radiation dose estimations were computed to link exposure and bioaccumulation with radiation dose. Cobalt (Co, non-radioactive) was selected as an environmentally relevant toxicant for investigation of genotoxicity and effects on reproductive success with a focus on male fish. Chronic exposure (12-d) to 0 – 25 mg l-1 Co resulted in reduced numbers of spawned eggs, lower fertilization success, and reduced survival of larvae to hatching. In male fish, DNA damage was detected in sperm and genes involved in DNA repair (xrcc5, xrcc6, and rad51) were induced in testes from some Co treatments, generally consistent with reduced reproductive success. No change in expression of repair genes in larvae spawned from parents exposed to Co was observed. Overall, results indicate that DNA damage and induction of DNA repair genes can occur rapidly after exposure to genotoxicants and that, if exposure levels are elevated, negative effects on reproduction can occur. Results are considered with particular focus on implications of male genotoxicity on reproductive success and the potential for transgenerational effects of toxicants.