Chemical Enhancers and Inhibitors of Carcinogenesis

A variety of chemicals can alter the course of oncogenesis in fish by acting as cocarcinogens, promoters, or anticarcinogens (Bailey et al., 1987). Certain pollutants seem to be involved in increasing the prevalence of neoplasms in fish, but in many cases it is not known whether these chemicals act as carcinogens, promoters, cocarcinogens, or as activators of oncogenic viruses. Some chemicals are probably both carcinogens and promoters; an initial exposure causes genetic change and continuing exposure stimulates development and growth of the neoplasm.

Metcalfe and Sonstegard (1985) demonstrated that pollutants can act as cocarcinogens. They injected rainbow trout embryos simultaneously with AFB1 and an extract of oil refinery effluent; after a year the frequency of neoplasms was higher in fish from this treatment than for fish that received only AFB1. Cocarcinogenic activity of the extract did not increase the carcinogenicity of MNNG, a direct-acting carcinogen.

Dietary treatment of rainbow trout with indole-3-carbinol, b-naphtho-flavone, or Aroclor 1254 before and during exposure to AFB1 reduces the incidence of hepatocellular carcinomas compared with fish receiving only AFB1 (Shelton et al., 1983; Nixon et al., 1984; Goeger et al., 1988). In contrast, when indole-3-carbinol or b-naphthoflavone was given after exposure to AFBj, the percentage of fish with carcinomas increased (Goeger et al., 1988; Dashwood et al., 1991). Carcinogenicity was also enhanced when 17b-estradiol, indole-3-carbinol, b-naphthoflavone, DDT, or dehydroepiandrosterone was fed to fish after a single exposure to AFB1 or MNNG (Nunez et al., 1988, 1989; Orner et al., 1995). A synergistic response occurred after simultaneous treatment of rainbow trout with Aroclor and diethylnitrosamine (DEN) (Shelton et al., 1984).

Maternal transfer of pollutants to offspring can also affect carcinogenesis. Aroclor 1254 was present in embryos after this PCB was fed to female rainbow trout for 2 months before spawning (Hendricks et al., 1981). After embryoexposure to AFB1, incidence of hepatocellular carcinoma was enhanced by maternally derived PCB.

The promotional activity of 41 agents was tested with a strain of hybrid Xiphophorus that was genetically predisposed to melanoma (A. Anders et al., 1991a). Thirty of these agents were positive, including the carcinogens MNU and A-ethyl-A-nitrosourea, and 11 were negative. Chemicals that were negative for promoting activity in this test included DEN.

Carbon tetrachloride enhances hepatocarcinogenesis in rainbow trout given a single injection of AFBi (Kotsanis and Metcalfe, 1991). The CCl4 was administered intraperitoneally at 21-day intervals starting 25 days after yolk-sac larvae were injected with AFB1. After 3 months, incidence of carcinomas in fish receiving both CQ4 and AFB1 was double the rate for fish injected with only AFB1. However, after 6 months there was no significant difference between these treatments.

Hydrogen peroxide in the diet enhances carcinogenicity in MNNG-initiated rainbow trout (Kelly et al., 1992). Fish fed H2O2 had increased levels of the mutagenic DNA adduct 8-hydroxy-2'-deoxyguanosine, which is an indication of oxidative DNA damage. Vitamin E, an antioxidant, did not have a significant effect in this study.

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