Carcinogens mouse liver

Herren-Freund SL, Pereira MA, Khoury MD, et al. 1987. The carcinogenicity of trichloroethylene and its metabolites, trichloroacetic acid and dichloroacetic acid, in mouse liver. Toxicol Appl Pharmacol 90 183-189. 

The role of N-sulfonyloxy arylamines as ultimate carcinogens appears to be limited. For N-hydroxy-2-naphthylamine, conversion by rat hepatic sulfotransferase to a N-sulfonyloxy metabolite results primarily in decomposition to 2-amino-l-naphthol and 1-sulfonyloxy-2-naphthylamine which are also major urinary metabolites and reaction with added nucleophiles is very low, which suggests an overall detoxification process (9,17). However, for 4-aminoazobenzene and N-hydroxy-AAF, which are potent hepatocarcinogens in the newborn mouse, evidence has been presented that strongly implicates their N-sulfonyloxy arylamine esters as ultimate hepatocarcinogens in this species (10,104). This includes the inhibition of arylamine-DNA adduct formation and tumorigenesis by the sulfotransferase inhibitor pentachlorophenol, the reduced tumor incidence in brachymorphic mice that are deficient in PAPS biosynthesis (10,115), and the relatively low O-acetyltransferase activity of mouse liver for N-hydroxy-4-aminoazobenzene and N-OH-AF (7,114,115). 

Boberg, E.W., Miller, E.C., Miller, J.A., Poland, A. Liem, A. (1983) Strong evidence from studies with brachymorphic mice and pentachlorophenol that I -sulfooxy safrole is the major ultimate electrophilic and carcinogenic metabolite of 1 -hydroxysafrole in mouse liver. Cancer Res., 43,5163-5173... 

Banerjee, S., Sharma, R., Kale, R.K. and Rao, A.R. (1994) Influence of certain essential oils on carcinogen-metabolizing enzymes and acid-soluble sulfhydryls mouse liver. Nutrition and Cancer 21, 263-269. 

Microcystins do not seem to be genotoxic, but they do have carcinogenic activity as demonstrated in various rat and mouse studies. For example, Ito et al. (1997) demonstrated that neoplastic nodules were induced in mouse liver by repeated intraperitoneal injections of MC-LR, and Humpage et al. (2000) detected an increase in the area of aberrant colon crypt foci in the mouse after chronic oral ingestion of MC for several months. In the same way, nodularin may have hepatic tumorigenicity, as detected in rats by Ohta et al. (1994). 

It shows mutagenic properties after activation. It is carcinogenic by various routes in the rat and mouse (liver carcinoma). By the oral route, it causes carcinoma of the bladder and lungs. Its carcinogenic action is influenced by diet. It is shown to be teratogenic. The LD50 in the rat is 200 mg kg orally and 230 mg kg intraperitoneally. The LD50 in the mouse is 300 mg kg orally and 230 mg kg intraperitoneally. 

EC Miller, JA Miller, EW Boberg, KB Delclos, CC Lai, TR Fennell, RW Wiseman, A Liem. Sulfuric acid esters as ultimate electrophilic and carcinogenic metabolites of some alkenylbenzenes and aromatic amines in mouse liver. Carcinog Compr Sury 10 93—107, 1985. 

Kerklaan P, Bouter S, Mohn G. 1983. Activation of nitrosamines and other carcinogens by mouse-liver S9, mouse hepatocytes and in the host-mediated assay produces different mutagenic responses in Salmonella TA 1535. Mutat Res 110 9-22. 

Quintero-Ruiz A, Paz-Neri LL, Villa-Trevino S. 1981. Indirect alkylation of CBA mouse liver DNA and RNA by hydrazine in vivo-. A possible mechanism of action as a carcinogen. J Natl Cancer Inst 3 613-618. 

The perfect fit of Haber s rule to the carcinogenic action of dieldrin in mouse liver provided no evidence of a subthreshold dose. Therefore, nongenotoxic carcinogens should not be assumed to exhibit a threshold per se rather they must be evaluated with regard to mode of action and human relevance, as discussed in Chapter 13. 

The oncogenicity concerns with chlordane persisted until Velsicol and EPA negotiated a voluntary cancellation of most of the termiticide uses in 1987 and avoided a cancellation hearing. The cancellation hearing was expected to be hard fought, as the evidence of carcinogenicity was based on mouse liver tumors, which provided evidence of a very different weight in 1987 than in 1979. 

Pereira MA. 1985. Mouse liver tumor data assessment of carcinogenic activity. In An International Symposium on Advances in Health Risk Assessment for Systemic Toxicants and Chemical Mixtures. Toxicol Ind Health 1(4) 311-334... 

Dr. Williams dwelt on the polychlorinated compounds that elicit tumors in rodents, mouse liver being the particular target and, occasionally, the thyroid. It seemed clear that these were epigenetic carcinogens that did not form covalent adducts with DNA nor damage DNA. Various tests for unscheduled DMA synthesis, point mutations and neoplastic transformation were all negative. Tests for promotional effect, in systems that revealed phenobar-bital to be a prototype promoter, served to establish that the chlorinated pesticides acted in the same way. Possible mechanisms of promoting action were reviewed. 

Rusyn, I. et al.. Expression of base excision repair enzymes in rat and mouse liver is induced by peroxisome proliferators and is dependent upon carcinogenic potency. Carcinogenesis, 21 (12), 2141,2000. 

Because of its carcinogenic activity in mouse liver, tetrachloroethylene has been tested for initiating and promoting activity in a rat liver foci assay. Tetrachloroethylene administered by gavage in com oil at 995 mg/kg/day did not exhibit initiating activity as indicated by an increase in -glutamyltranspeptidasepositive type I altered foci. Tetrachloroethylene did promote the appearanee of type II altered foci, both in the presence and in the absence of an initiator (in this case, diediylnitrosamine) (Story et al. 1986). 

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