Carcinogenesis immune function

CJ Portier NIEHS Increase the use and application of mathematical and statistical models in toxicology and biochemistry and to implement new mathematical models to help explain current research findings relating to carcinogenesis and suppressed immune function following exposure to toxicants such as 2,3,7,8-TCDD... 

The research on CLA in growing animals is consistently showing effect on modulation of body mass and fat, however, the effect in humans is not consistent. More research is needed to delineate the effect of CLA and isomers on body composition in humans. Major research emphasis, at present, is focused on the effects of CLA and its isomers on body composition and carcinogenesis. Other areas that are attracting attention include the effects of CLA and isomers on cardiovascular, metabolic, and immune functions and the strategies to increase the content of CLA isomers in meat and dairy products. 

Carcinogenic PAHs have been suggested to have an effect on immune function (Luster and Rosenthal 1993 Saboori and Newcombe 1992), thereby allowing the induction of carcinogenesis, while noncarcinogenic PAHs do not affect immue function (see Section 2.4). The effects of dermally applied benzo[a]pyrene alone or following dermal pretreatment with the prostaglandin synthetase inhibitor, indomethacin, on contact hypersensitivity (cell-mediated immunity), production of antibodies to DNP (humoral immunity), and the induction of skin tumors was studied in male BALBc... 

Benzo[a]pyrene has also been shown to affect immune responses to viral infection. Benzo[a]pyrene can reversibly inhibit the induction of viral interferon in 32 different mammalian cell lines but only in the presence of S9 metabolic activation (Hahon and Booth 1988). This inhibition must occur at an early level and not affect viral interferon interactions because the activity of exogenous interferon was unaffected. In addition, influenza virus multiplication was also inhibited by activated benzo[a]pyrene. Benzo[e]pyrene had no effect on interferon induction. The authors suggest that benzo[a]pyrene s inhibition of interferon induction may be an early step in compromising the host s immune function, thereby allowing the induction of carcinogenesis. 

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... 

It is clear from the above discussion that alterations in dietary lipid intake can profoundly affect cell membrane composition in human skin, and consequently influence many physiological and pathological processes. While deficiency of LA results in loss of barrier function and hyperproliferation, an altered n-3 and n-6 EFA balance may influence many processes including a wide range of inflammatory and immune responses, and skin carcinogenesis. There is evidence that alterations in eicosanoid production may contribute to many of the activities, while there is also an increasing understanding... 

If the mechanistic information just discussed in Fig. 7.1 is to be really useful then it must be an intrinsic property of the chromophores themselves, i.e. the two ethylene molecules. For example, it is the key feature in intra-strand thymine dimerisation and these dimers can disrupt the function of DNA and trigger complex biological responses, including apoptosis, immune suppression, and carcinogenesis. One can identify the geometry corresponding to the point E in Fig. 7.1 as well as the computed directions [20] Xi and X2 for the 2-1-2 cyclo-addition reaction of two thymine molecules. 

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