Tumors, induction

Nitrosamines are readily produced from the reaction of amines with nitrous acid, i.e., acidified nitrite (3), and are also produced vivo when amines and nitrite are administered, as reflected by tumor induction [reviewed in (3)], and the in vivo appearance of nitrosamines (2> ) Challis and Kyrtopoulos (5) showed that gaseous NO2 reacts directly with amines in neutral or alkaline aqueous solutions to produce nitrosamines and nitramines. The kinetics of the extremely rapid reaction of... 

Lloyd RD, Taylor GN, Jee WSS, et al. 1999. Relative radiosensitivity of bone tumor induction among beagles as a function of age at injection of 239Pu or 226RA. Health Phys 76(l) 75-81. 

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. 

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. 

The choice of species and strain to be used in a carcinogenicity study is based on various criteria including susceptibility to tumor induction, incidence of spontaneous tumors, survival, existence of an adequate historical data base, and availability. 

Susceptibility to tumor induction is an important criterion. There would be little justification for doing carcinogenicity studies in an animal model that did not respond when treated with a true carcinogen. Ideally, the perfect species/strain would have the same susceptibility to tumor induction as the human. Unfortunately, this information is usually unavailable, and the tendency has been to choose animal models that are highly sensitive to tumor induction to minimize the probability of false negatives. 

Humans can be exposed to POPs through diet, occupational exposures (for example, farmworkers may be exposed to POPs through pesticides), industrial accidents and the environment (including indoor exposure). Exposure to POPs, either acute or chronic, can be associated with a wide range of adverse health effects, including illness and death (L. Ritter et al., 1995). Laboratory animal studies and wildlife studies have associated POPs with endocrine disruption, reproductive and immune dysfunction, neurobehavioral disorders and cancer. More recently, some POPs have also been connected to reduced immunity in infants and children and a concomitant increase in infections. Other studies have linked POPS concentrations in humans with developmental abnormalities, neurobehavioral impairment and cancer and tumor induction or promotion.4... 

Pliss, G.B. and Khudoley, V.V. Tumor induction by carcinogenic agents in aquarium fish. J. Matl. Cancer Inst. (1975) 55, 129-136. 

Van Duuren BL, Blazej T, Goldschmidt BM, et al. 1971. Cocarcinogenesis studies on mouse skin and inhibition of tumor induction. J Natl Cancer Inst 46 1039-1044. 

In order to prove the efficiency of the liposomal system in tumor therapy (administration of the liposomes after tumor induction), seven animals were treated with 2 x 10 B16 tumor cells (injection of a suspension in 200 pL HBSS into tail vein). After four and seven days the formulation [AVE 3 TRP-2 (10 pg TRP-2) and AVE 3 1826 CpG (1.3 pg CpG)] was given into the foot pad of the hind legs of the mice intradermally. Twenty-one days after the injection of the tumor cells, the animals were sacrificed and the metastases in the prepared lungs were counted. A second group of seven animals received the tumor cells, but no liposomal treatment was applied. Table 2 indicates the high antitumor potency of the formulation. 

In another study by Larson et al. (1994d) the possible relationships among chloroform-induced cytolethality, regenerative cell proliferation, and tumor induction were identified in male B6C3Fi mice dosed with chloroform by gavage in com oil. Mice received chloroform at doses of 0, 34, 90, 138, or 277 mg/kg/day for 5 days a week for 3 weeks. To monitor cell proliferation, mice were administered BrdU... 

W. K. Lutz and A. Kopp-Schneider, Threshold dose response for tumor induction by genotoxic carcinogens modeled via cell-cycle delay. Toxicological Sciences, 1999,49(1), 110-115. 

Positive carcinogenic findings in animals require careful evaluation to determine their relevance to humans. Of key importance is the mechanisms/mode(s) of action of tumor induction. The WHO/IPCS has developed a conceptual framework to provide a strucmred and transparent approach for the assessment of the overall weight of evidence for a posmlated mode of induction for each mmor type observed (Sonich-Mullin et al. 2001). The framework promotes confidence in... 

The T25 approach was discussed at a workshop organized by the European Centre for the Ecotoxicologicy and Toxicology of Chemicals (ECETOC) (Roberts et al. 2001, ECETOC 2002). It was concluded that the use of the T25 method in risk assessment is problematic due to uncertainties arising from the false assumption of both precision and linearity in the dose-response curves for tumor induction. 

Biegel LB, Hurtt ME, Lrame SR, et al Mechanisms of extrahepatic tumor induction by peroxisome proliferators in male CD rats. Toxicol Sci 60 44-55, 2001... 

In addition to tumor induction and cyto-genic damage, inhaled benzene in mice can cause immunodepressive effects at 100 ppm as manifested by reduced host resistance to a transplantable syngeneic tumor. "... 

Stoner GD, You M, Morgan MA, et ah Lung tumor induction in strain A mice with hen-zotrichloride. Cancer Lett 33 167-73, 1986... 

A number of animal studies suggest that hepatomas occur only after liver necrosis and fibrosis have occurred and, therefore, that carbon tetrachloride is not a direct liver carcinogen." One early study, however, found that liver necrosis and its associated chronic regenerative state probably were not necessary for tumor induction, although a correlation was found between the degree of liver necrosis and the incidence of hepatomas. "... 

Fukumura D, Xavier R, Sugiura T, et al. Tumor induction of VEGF promoter activity in stromal cells. 

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