Enzyme altered foci

Story DL, Meierhenry EF, Tyson CA, et al. 1986. Differences in rat liver enzyme-altered foci produced by chlorinated aliphatics and phenobarbital. Toxicol Ind Health 2 351-362. 

Flodstrom, S., L. Wamgard, S. Ljungquist, and U.G. Ahlborg. 1988. Inhibition of metabolic cooperation in vitro and enhancement of enzyme altered foci incidence in rat liver by the pyrethroid insecticide fenvalerate. Arch. Toxicol. 61 218-223. 

Columbano A, Ledda-Columbano GM, Ennas MG, et al. 1990. Cell proliferation and promotion of rat liver carcinogenesis different effect of hepatic regeneration and mitogen induced hypoerplasia on the development of enzyme- altered foci. Carcinogenesis 11 4771-776. 

Rezabek MS, Sleight SD, Jensen RK. 1987. Short-term oral administration of polybrominated biphenyls enhances the development of hepatic enzyme-altered foci in initiated rats. J Toxicol Environ Health 20 347-356. 

Stenius, U., Warholm, M., Raimug, A., Walles, S., Lundberg, 1. Hogberg, J. (1989) The role of glutathione depletion and toxicity in hydroquinone-induced development of enzyme-altered foci. Carcinogenesis, 10, 593-599... 

Rat. In a rat liver foci assay for tumour-initiating activity, groups of 10 male Osborne-Mendel rats were subjected to a two-thirds partial hepatectomy and, 24 h later, were given 1,1,2,2-tetrachloroethane or com oil by gavage at the maximum tolerated dose in com oil. Six days after partial hepatectomy, rats received 0.05% phenobarbital in the diet for seven weeks, then control diets for seven further days, after which they w ere killed and their livers were examined. The numbers of enzyme-altered foci in the liver were 0.41 0.31 and 0.26 0.19 foci/cm in the test and control (com oil) groups, respectively. It was concluded that 1,1,2,2-tetrachloroethane did not show- initiating activity in this system (Milman et al., 1988). 

In a promotion study, groups of 10 rats were given an intraperitoneal injection of 30 mg/kg bw A-nitrosodiethylamine (NDEA) 24 h after a two-thirds partial hepatectomy. Six days later, the rats received 1,1,2,2-tetrachloroethane in com oil at the maximum tolerated dose or com oil by gavage on five days per week for seven weeks. The rats were held for an additional seven days and then killed and the livers were examined. The numbers of enzyme-altered foci were 4.36 0.85 foci/cm- in the treated group and 1.77 0.49 foci/cm2 in the control (com oil) group, indicating that 1,1,2,2-tetrachloroethane shows promoting activity (Milman et al., 1988). 

Induction of hepatic enzyme-altered foci (ATPase, GGTase) was investigated after administration of vinyl acetate (200 and 400 mg/kg/day, orally) to newborn rats for 3 weeks, with or without subsequent promotion by phenobarbital (57). No foci were observed in vinyl acetate-treated animals at the age of 14 weeks, whereas the structurally related compounds vinyl carbamate and vinyl chloride induced enzyme-altered foci under comparable experimental conditions. The negative result was not surprising considering the short exposure period and relatively low doses compared to the carcinogenicity studies discussed above. 

Laib RJ, Bolt HM. 1986. Vinyl acetate, a structural analog of vinyl carbamate, fails to induce enzyme-altered foci in rat liver. Carcinogenesis 7 841—43... 

Barrow BJ, O Riordan MA, Stellato TA, et al. 1990. Enzyme-altered foci in colons of carcinogen-treated rats. Cancer Res 50 1911-1916. 

Dock L, Scheu G, Jernstrom B, et al. 1988. Benzo[a]pyrene metabolism and induction of enzyme-altered foci in regenerating rat liver. Chem Biol Interact 67(3-4) 243-253. 

Luebeck EG, Moolgavkar SH, Buchmann A, et al. 1991. Effects of polychlorinated biphenyls in rat liver Quantitative analysis of enzyme-altered foci. Toxicol Appl Pharmacol 111 469-484. 

Pereira MA, Herren SL, Britt AL, et al. 1982. Promotion by polychlorinated biphenyls of enzyme-altered foci in rat liver. Cancer Lett 15 185-190. 

Campbell, H. A., Xu, Y. D., Hanigan, M. H., and Pitot, H. C. (1986). Application of quantitative stereol-ogy to the evaluation of phenotypically heterogeneous enzyme-altered foci in the rat liver. J Natl Cancer Inst 76(4), 751-767. 

The analysis of experiments that measure the number and size of premalignant lesions in animals exposed to carcinogenic agents is possibly the purest application of multistage models to the investigation of promotion. In particular, the mathematical expressions discussed in Section 25.1.6 have been used extensively to analyze experimental data on enzyme-altered foci (EAF) in the rat liver. EAFs are clonal... 

It was reported that DEN-initiated enzyme-altered foci develop to form hepatocellular carcinomas [16]. However, it was reported that the vast majority of foci and hyperplastic nodules disappear after removal of the animals from the carcinogenic diet [17]. In the present series of experiment, we administered PB as a promoter continu-... 

The mechanism of action of drug induced hepatocellular tumors is quite similar to epidermal carcinogenesis. There are a series of biochemical changes such as enzyme induction that are parallel in liver and skin. Hyperplastic nodules result from promoter treatment and these nodules regress if the promoting stimulus is removed up to a critical point, after which the nodule is committed to develop into a hepatoma. The preneoplasic nodules contain enzyme altered foci for y-glutamyltranspeptidase, canalicular ATPase, glu-cose-6-phosphatase and iron deficient foci (Pitot et al., 1982). It is not clear whether or not all of the enzyme alTered foci result in hepatomas but they are certainly direct evidence of enhanced clonal growth or cell section and proliferation of presumably initiated cells. The promotional model can be modified by hormonal and dietary factors and this model has potential use for extrapolation to the human population. 

---