Graduate Thesis Or Dissertation
 

Temperature-modulated 7,12-dimethylbenz(a)antheracene carcinogenicity in rainbow trout

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  • Temperature influences the incidence of chemically induced cancer in fish, with warmer temperatures being associated with higher cancer incidence. The mechanisms of temperature-modulated chemical carcinogenesis in fish, however, have not been described in detail. Therefore, one primary objective of this study was increased understanding of how temperature-modulated genotoxicity of 7,12- dimethylbenz(a)anthracene (DMBA) corresponded with tumor response. The second entails the potential of temperature to modulate cancer promotion. Rainbow trout (Oncorhyncus mykiss) (2 g) were acclimated at 10, 14 or 18°C for one month and then exposed to 1.0 ppm DMBA in their water for 20 hr. Exposures were at respective acclimation temperatures or 10 and 18°C acclimated fish were shifted to 14°C for DMBA exposures. Adduction of [³H]DMBA to hepatic DNA 21 days after exposure was higher in 10°C than 18°C fish exposed at their respective acclimation temperatures. However, in fish shifted to 14°C, the concentration of hepatic [³H]DMBA DNA adducts was similar in 10°C and 18°C acclimated fish at that time. Temperature effects on tumor incidence were assessed 9 months after DMBA waterborne exposures. Incidence of stomach, liver and swim-bladder cancer increased with rearing temperature. Differences in tumor incidence were less marked in fish reared at the same temperature (14°C). Retrospective analyses of livers from a tumor study initiated with aflatoxin B1 (AFB1) was conducted with antibodies to endogenous proliferating nuclear antigen (PCNA). Proliferating cells were scored by counting labeled nuclei in 5 random 10x fields using an image analysis program (BIOQUANT SYSTEM IV). There was no significant increase in numbers of PCNA labeled hepatocytes with temperature. The influence of acclimation temperature on plasma mitogens that stimulate cell division was assessed in cultured Chinook salmon embryo cells (CHSE-214). Plasma from rainbow trout (120-150 g) acclimated to either 10 or 18°C for at least four weeks stimulated in vitro proliferation of CHSE-214 cells to the same extent. This study demonstrated that chemically induced tumors in fish were modulated by temperature not only through genotoxin disposition and formation but also through persistence of DNA adducts. It also discounted the role of mitogenesis in temperature-modulated chemical carcinogenesis.
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