Rat liver 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. 

Groups of 7-10 male Sprague-Dawley rats, weighing 200 g, were administered catechol (purity, > 98%) at concentrations of 0 or 100 mg/kg in the diet for six weeks beginning one week after partial hepatectomy and intraperitoneal injection of 30 mg/kg bw /V-nitrosodietliylamine to initiate liver carcinogenesis. Catechol after initiation did not increase the multiplicity of liver enzyme-altered (y-glutamyltranspeptidase) foci (Stenius et al., 1989). 

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). 

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... 

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... 

Marayama, H., Tanaka, T. Williams, GM. (1990) Effects of the peroxisome proliferator di(2-ethylhexyl)phthalate on enzymes in rat liver and on carcinogen-induced liver altered foci in comparison to the promoter phenobarbital Toxicol. Pathol., 18, 257-267 Matsushima, T, Muramatsu, M. Haresaku, M. (1985) Mutation tests on Salmonella typhimurium by the preincubation method. Prog. Mutat. Res., 5, 181-186 Matthews, E.J., DelBalzo, T. Rundell, J.O. (1985) Assays for morphological transformation and mutation to ouabain resistance of Balb/c-3T3 cells in culture. Prog. Mutat. Res., 5, 639-650... 

Some information on structure-promotion relationships for PBBs is available from studies that used two-stage liver and skin carcinogenesis models. In the liver promotion studies, development of enzyme-altered hepatic foci (putative preneoplastic lesions) was assessed in rats that were partially hepatectomized, initiated with diethylnitrosamine and promoted with PBBs (Buchmann et al. 1991 Dixon et al. 1988 ... 

GerbrachtU, Einig C, Oesterle D, et al. 1990. Di(2-ethylhexyl)phthalate alters carbohydrate enzyme activities and foci incidence in rat liver. Carcinogenesis 11 (12) 2111-2115. 

Hepatic Effects. The induction of foci of altered hepatocytes is often seen in rats and mice that also develop liver tumors. These foci have altered enzyme activities and higher rates of cell proliferation than normal hepatocytes. A 1-day intragastric administration of 200 mg/kg of benzo[a]pyrene or dibenz[a,h]anthracene, or of 180 mg/kg benz[a]anthracene to rats was followed by a diet containing... 

Laib RJ, Rose J, Brunn H. 1991. Hepatocarcinogenicity of PCB congeners I. Initiation and promotion of enzyme-altered rat liver foci by 2,2, 4,5 -tetra- and 2,2, 4,4, 5,5 -hexachlorobiphenyl. Toxicol Environ Chem 34 19-22. 

Moolgavkar, S. H., Luebeck, E. G., Buchmann, A., and Bock, K. W. (1996). Quantitative analysis of enzyme-altered liver foci in rats initiated with diethylnitrosamine and promoted with 2,3,7,8-tetrachlorodibenzo-jtj-dioxin or 1,2,3,4,6,7,8-heptachlorodibenzo-jtJ-dioxin. Toxicol Appl Pharmacol 138, 31-42. 

Hagiwara, A. Tanaka, H. Kurata, Y Kato, T. Tsuda, H. Ito, N. Lack of hepatotoxicity or promotion of enzyme-altered liver foci development in rats treated with harman or norharman. J. Toxicol. Environ. Health 1990, 29, 211-218. 

Two studies were located in which rats received di- -octylphthalate dietary exposures of 250 or 500 mg/kg/day for either 10 or 26 weeks (Carter et al. 1992 DeAngelo et al. 1986). Five male rats were first initiated with a single subcarcinogenic intraperitoneal dose of diethylnitrosamine (30 mg/kg), followed by partial hepatectomy. Di-w-octylphthalatc caused substantial increases in gamma-glutamyltranspeptidase (GGT) positive liver foci when compared with the controls (e.g., from 3.5 to 20.8 foci/cm2) or in hepatic levels of marker enzymes for altered cellular foci (GGT and glutathione 5-transferase [GST]). Only a slight increase (threefold) was observed for carnitine acetyltransferase (CAT) activity, a marker for peroxisome... 

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