Liver regeneration is induced by heat stress in the small viviparous fish, Poeciliopsis. Acute exposure to sublethal temperatures, one to two degrees below their killing temperature, damages tissue and initiates liver cell proliferation in P. lucida, P. monacha, and P. monacha-lucida hybrid clones, SYN-4 and SYN-5. Regeneration of liver cells began within 1–2 days following heat stress and proceeded over 5 days. Peak cell proliferation occurred 2–3 days after treatment in fish of all four genotypes. Cell proliferation was induced in the two all-female clones, SYN-4 and SYN-5, by exposure to 40.5° C for 60 minutes. This treatment imposed mortalities of 17.9% and 16.7%, respectively, whereas reduction of the temperature to 39.5°C and reduction of the time to 30 minutes resulted in no mortalities without significantly lowering the level of cell proliferation (p > 0.05). Liver cell proliferation induced by both heat treatments was significantly higher (p < 0.05) in the SYN-5 hybrids than in SYN-4. The induction of liver cell proliferation with sublethal temperature exposures is discussed as it may relate to chemical carcinogenesis in both feral and laboratory fish. Acute heat exposure may be used experimentally in fish as an independent stimulus for liver cell proliferation in carcinogenesis studies. In poikilothermic animals-heat exposure offers an alternative to surgical removal of approximately two-thirds of the liver, the method most frequently used in rodents to study the process of liver regeneration.
The viviparous fish Poeciliopsis from northwestern Mexico is characterized according to its potential in cancer research. A colony of these fishes started in 1961 includes inbred strains of P. lucida (M61-9, M61-31, M61-35, and S68-4), P. monacha (S68-4 and S68-5), and P. viriosa (M65-23), which have been demonstrated by electrophoresis and tissue graft analysis to be homozygous. All-female species of hybrid origin are represented by 12 clones which, although highly heterozygous, are genetically identical or isogenic and readily accept within-clone tissue transplants. Two studies are cited in which hepatic tumors were chemically induced. In one, liver neoplasms were induced in P. lucida and P. monacha by repeated short-term exposures to an aqueous suspension of 5 ppm 7,12-dimethylbenz[a]anthracene. In the other, dose responses to the carcinogen diethylnitrosamine (DENA) were compared among 4 inbred strains, 3 hybrids from crosses between inbred strains, and 2 wild stocks of P. lucida. The incidence of hepatic tumors gradually increased from 0 to 93% depending on the concentration of the compound and the number of exposures, but no significant difference was found among the inbred strains, their hybrids, or the wild stocks. Hepatic tumors, initially induced with DENA have been successfully transplanted into the muscle tissue and abdominal cavity of members of the same strain.
Liver neoplasms were induced in two species of viviparous fishes, Poeciliopsis lucida and P. monacha, by repeated short-term exposures to an aqueous suspension of 5 ppm 7,12-dimethylbenz[a]anthracene (DMBA). Predominantly hepatocellular neoplasms developed in 47 out of 106 fish surviving the period allowed for tumor development, 6–9 months after initial exposure to DMBA. The use of short-term exposure periods of 6 hr in young fish and up to 20 hr in adults reduced stress and mortalities caused by the toxicity of DMBA at 5 ppm. A lower concentration of DMBA, 0.25 ppm, failed to induce tumors in any of the surviving 230 of 295 young fish administered repeated 20-hr exposures. This study shows for the first time that DMBA is carcinogenic to fish.