Immune response, carcinogenic cells

Interferons (lENs) (52,53), a family of species-specific vertebrate proteins, confer nonspecific resistance to a broad range of viral infections, affect cell proliferation, and modulate immune responses. AH three principal interferons, a-interferon (lEN-a) produced by blood leucocytes, P-interferon (lEN-P) by fibroblasts, and y-interferon (lEN-y) by lymphocytes, also have antiviral activity. The abiUty of interferons to inhibit growth of transplantable and carcinogen-induced tumor led to research showing the direct antiproliferative and indirect immune-mediated antitumor activities (see Chemotherapeutics, anticancer). IENs have been found to be efficacious in certain malignancies and viral infections, eg, hairy cell leukemia (85% response) and basal cell carcinoma (86% response). However, the interferons do have adverse side effects (54). 

The most characteristic toxic effect of benzene in both human and animal models is the depression of the bone marrow, leading ultimately to aplastic anemia (Rozen and Snyder 1985 Snyder and Kocsis 1975 Snyder et al. 1993b). Rozen and Snyder (1985) have noted that abnormalities of humoral and cell-mediated immune responses following benzene exposure of C57BL mice by inhalation are presumably caused by a defect in the lymphoid stem cell precursors of both T- and B-lymphocytes. They also observed that bone marrow cellularity and the number of thymic T-cells increased, presumably as a compensatory response in these cell lines in response to benzene exposure. This compensatory proliferation may play a role in the carcinogenic response of C57BL mice to inhaled benzene. 

Other defense mechanisms are also available. Cells have effective transport systems which pump out foreign chemicals. Our cells are very good at repairing chemically damaged DNA (deoxyribonucleic acid see Chapter 9 for a more detailed discussion of DNA) and even this event is not fatal. Only when the capacity for the cell to repair itself is overwhelmed does disease result. Again, dose is the determining factor. Finally, if all else fails, cells that become carcinogenic often induce an immune response to themselves and are eliminated by this route. When these mechanisms have been exhausted, or, in the case of extreme age, when they have become worn out, disease occurs. 

The disturbances in protein phosphorylation patterns in Cr(VI) treated cells are considered among the possible reasons for Cr(VI) toxicity and carcinogenicity (295, 626). The question then arises, as to whether the proposed beneficial action of Cr(III) in activation of insulin receptor tyrosine kinase (496,497) is, in fact, a sign of Cr(III) toxicity (5). Unpredictable changes in the concentrations of phosphorylated proteins in the presence of excess Cr(III) may lead to abnormalities in the cell signaling pathways and ultimately to cancer (5). An answer to this dilemma may lie in selectivity studies (which are yet to be performed) of different types of Cr(III) complexes toward various kinases or phosphatases. Clearly, the Cr(III) complexes of potential use as anti-diabetics should be highly selective in the activation of protein tyrosine kinase of the p-subunit of the insulin receptor (496, 497). On the other hand, the potential ability of some Cr(III) complexes to selectively activate non-insulin dependent protein kinases may lead to beneficial effects, such as stimulation of immune responses or antitumor activity (627, 628). 

The diet is believed to play an important role in the onset of carcinogenesis, and there are a number of carcinogens present in food, including mycotoxins, polycyclic hydrocarbons, and pesticides. Associations have been made between dietary fat intake and morbidity and mortality from breast and colon cancer. Another possible mechanism for the proposed protective effects against cancer of olive oil compared with sunflower oil involves diet-induced alterations in host immune responses. Both the type and concentration of dietary fats have been reported to influence immune status in several animal models. The PUFA Cigtz is necessary for T-cell-mediated immunity, but high intakes will suppress immune function and may therefore increase the risk of cancer. Furthermore, comparisons between the effects of diets rich in Ci8 2 and those rich in Cig i on varying indicators of immune function in mice have shown that, while dietary Ci8 2 predisposed... 

The specific mechanisms by which individual dietary components can alter the cancer process remain poorly understood. However, mechanisms underlying the carcinogenesis process are understood sufficiently so that model systems to evaluate the ability of a specific compound to inhibit or promote processes that may prevent or delay cancer development can be predicted. Phytochemcials can act at a variety of sites relevant to the development of the cancer cells. They may inhibit carcinogen activation, induce hepatic detoxification pathways, exert antioxidant effects/metal chelation properties, enhance immune response, induce apoptosis, and alter hormonal environment. 

A number of bacterial and host factors contribute to the ability of HP to cause gastroduodenal mucosal injury. Pathogenic mechanisms include (a) direct mucosal damage, (b) alterations in the host immune/inflammatory response, and (c) hypergastrinemia leading to increased acid secretion. In addition, HP enhances the carcinogenic conversion of susceptible gastric epithelial cells. ... 

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