Tumors induction in rats

Frankfurt OS, Lipchina LP, Bunto TV, Emanuel NM. 1967. [The effect of 4-methyl-2,6-di-tert.-butylphenol (ionol) on liver tumor induction in rats]. Biull Eksp Biol Med 64 86-88. 

ALPHA2U-GL0BULIN NEPHROPATHY AND CHRONIC PROGRESSIVE NEPHROPATHY AS MODES OF ACTION FOR RENAL TUBULE TUMOR INDUCTION IN RATS, AND THEIR POSSIBLE INTERACTION... 

Ranaldi, G., Mancini, E., Ferruzza, S., Sambuy, Y. Perozzi, G. (2007) Effects of red wine on ochratoxin A toxicity in intestinal Caco-2/TC7 cells. Toxicol. In Vitro 21, 204-210. Rasonyi, T. (1995) Mechanistic Investigations In ochratoxin A induced nephrotoxicity and their relevance for the sex specific renal tumor Induction in rats. Zurich, Switzerland, University of Zurich (Dissertation ETH No. 11343). 

Lock, E.A. and Hard, G.C. (2010) Alpha2u-globulin nephropathy and chronic progressive nephropathy as modes of action for renal tubule tumor induction in rats, and their possible interaction. In Cancer Risk Assessment—Chemical Carcinogenesis, Hazard Evaluation, and Risk Quantification, (Hsu, C.H. and Stedeford, T. Eds.), pp. 248-255, John Wiley Sons, Ltd., Oxford, England. 

Stober W, Morrow PE, Oberdorster G. Pulmonary retention of inhaled anatase (TiOj) aerosols and lung tumor induction in rats simulated by a physiology-oriented model. Inhal Toxicol 1995 7 1059-1074. 

Waalkes, M.P., S. Rehm, C.W. Riggs, R.M. Bare, D.E. Devor, L.A. Poirier, M.L. Wenk, and J.R. Henneman. 1989. Cadmium carcinogenesis in male Wistar [Crl (Wl)BR] rats dose-response analysis of effects of zinc on tumor induction in the prostate, in the testes, and at the injection site. Cancer Res. 42 4282-4288. 

Clifton, K.H. and Crowley, J.J. (1978). Effects of radiation type and dose and the rate of glucocorticoids, gonadectomy, and thyroidectomy in mammary tumor induction in mammotrophic-secreting pituitary tumor-grafted rats, Cancer Res. 38,1507. 

There are examples where PPARa activation does not consistently lead to liver cancer, and these have been summarized in Klaunig et al. (2003). Weak PPARa activators (i.e., compounds that minimally induce markers of PPARa activation) would not necessarily increase liver tumor incidence, because a sufficient level of receptor activation is needed for induction of key events (Klaunig et al. 2003). Pharmacokinetic differences between susceptible and nonsusceptible rodents that lead to differences in tissue chemical concentration could also contribute to discrepancies between the ability of chemicals to activate PPARa in trans-activation assays and tumor induction. For example, trichloroacetate (TCA) exposure in mice leads to increases in PCO activity at doses similar to or below those that induce liver tumors whereas in rats TCA, even at high doses, only marginally increases PCO in the absence of increases in liver tumors (Corton 2008). 

In rats administration of chemicals present in cigarette smoke after exposure to radon and radon daughters resulted in a decrease in the lung cancer latency period when compared to the time-to-tumor induction in animals treated with radon alone. This effect was seen with 5,6-benzoflavon (Queval et al. 1979) and with cerium hydroxide (Chameaud et al. 1974). 

G. L. Laqueur, E. G. McDaniel, and H. Matsumoto, Tumor induction in germfree rats with methylazoxymethanol (MAM) and synthetic MAM acetate, J. Natl. Cancer Inst. 39, 355-371 (1967). 

While there is some evidence of lung tumor induction in laboratory rat inhalation studies, more research is needed to evaluate carcinogenicity of different forms of antimony via oral routes of exposure. 

For example, 7,12-dimethylbenz[a]anthracene is a particularly potent carcinogen for the mammary gland of young female Sprague-Dawley rats after oral or intravenous administration (25,26), dietary benzo[a]pyrene leads to leukemia, lung adenoma and stomach tumors in mice (27), and either of these hydrocarbons can induce hepatomas in male mice when injected on the first day of life (28). Nevertheless, the mouse skin system has proved to be particularly valuable because of the rapidity of tumor induction, the ease of detection of tumors and because the multi-stage nature of the carcinogenic process was experimentally established in this system. 

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