Tumor formation

Health nd Safety Factors. Isophorone is considered moderately toxic by ingestion and skin contact. Some rat tumor formation evidence has been found (264), but no demonstration as a human carcinogen has been proven. Isophorone is considered an Environmental Protection Agency (EPA) priority pollutant, and has a permissible acute toxicity concentration of 117, 000 ///L to protect freshwater aquatic life, 12, 900 ///L to protect saltwater aquatic life, and 5, 200 ///L to protect human life (265). Isophorone is mildly toxic by inhalation, but because of its low volatiUty it is not a serious vapor hazard. 

Swallowing. If it is sufficiently irritant or caustic, a swallowed material may cause local effects on the mouth, pharynx, esophagus, and stomach. Additionally, carcinogenic materials may induce tumor formation in the alimentary tract. Also, the gastrointestinal tract is an important route by which toxic materials are absorbed. The sites of absorption and factors regulating absorption have been reviewed (42,43). 

Altered cell morphology Increased growth rate Increased saturation density Formation of multilayers Reduced adhesion to substratum Colony formation in soft agar Reduced serum requirement Altered growth factor requirement Tumor formation in athymic nude mice... 

In the last several years, there has been escalating interest in the idea that cancer stem cells play a central role in tumor formation and spread. The cancer stem cell... 

CCR2 expression was also examined in liver tumor formation induced by intraportal injection of a murine colon adenocarcinoma cell line (58). Tumor growth occurred at similar rates in wild-type and CCR2 /" mice, but the number... 

Yang X, Lu P, Ishida Y, Kuziel WA, Fujii C, Mukaida N. Attenuated liver tumor formation in the absence of CCR2 with a concomitant reduction in the accumulation of hepatic stellate cells, macrophages and neovascularization. Int J Cancer 2006 118 335-345. 

The importance of FAK is underlined by the finding that cells expressing a constitutively active form survive in suspension even though they are homeless. Here, the protein kinase is active regardless of the failure to make contact with an extracellular matrix. Rescue from apoptosis also occurs when cells express constitutively activated oncogenic forms of Ras or Src and thus activate Plj-kinase and the MAP kinase pathway. Unlike FAK, these not only prevent apoptosis but also promote proliferative signals that result in tumor formation. 

Goralczyk, R., Wertz, K., Lenz, B. et al. 2005. Beta-carotene interaction with NNK in the AJ-mouse model Effects on cell proliferation, tumor formation and retinoic acid responsive genes. Biochim Biophys Acta 1740 179-188. 

In a chronic study in rats (Quast et al. 1980a), some changes in the blood parameters measured were observed at various intervals during the study, but the findings did not occur consistently and were not dose-related. Therefore, the authors concluded that these findings were not direct effects of exposure to acrylonitrile, but rather were a secondary response to other effects such as weight loss, tumor formation, or inflammatory reactions. 

A number of research projects in progress are investigating the mechanism of toxicity and tumor formation of acrylonitrile. The projects are summarized in Table 2-6. 

So we are still left with two models of the stereochemistry of DNA alkylated by a PAH diol epoxide the PAH either lies in a groove of DNA or else tries to intercalate between the bass of DNA. Since it is covalently bonded to a base it must cause considerable distortion if it tries to lie between the bases. However, the stacking observed in the crystalline state seems to argue for partial intercalation. We will need crystal structures of at least one appropriately alkylated polynucleotide before this problem can be resolved. And when this is done it will be just the beginning of the answer to the problem of alkylation of DNA by activated carcinogens. The subsequent question is, what is the lesion in DNA that is important in carcinogenesis, and then what does it cause to happen so that tumor formation is initiated ... 

Condensation of coumaric acid with malonic acid yields the basic chalcone and stilbane skeletons (see Fig. 3.6). Stilbenes are found in most vascular plants, where they exhibit fungicidal and to a lesser extent antibiotic properties. They function as both constitutive and inducible defense substances. Some stilbenes inhibit fungal spore germination and hyphal growth, whereas others are toxic to insects and parasitic nematodes (round-worms). They also possess antifeeding and nematicide properties in mammals. For example, resveratrol (a stilbene in red wine) suppresses tumor formation in mammals. 

Enhanced tumor formation in rodent liver (Flodstrom et al. 1988)... 

In preclinical models of postmenopausal osteoporosis, lasofoxifene inhibited bone turnover and prevented bone loss throughout the skeleton (Maeda et al. 2004). The primary indication of lasofoxifene is the treatment and prevention of postmenopausal osteoporosis. In preclinical models, lasofoxifene inhibited breast tumor formation and reduced serum cholesterol (Maeda et al. 2004). Lasofoxifene-treated animals did not differ from ovariectomized controls with respect to endometrial thickness and superficial and basal endometrial gladular epithelial luminal area (Maeda et al. 2004 Ke et al. 2004). 

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