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Food Supplements as Activation Modulators of Food Carcinogens, Phase II Metabolism
Bebová, Michaela ; Hodek, Petr (advisor) ; Koblihová, Jitka (referee)
Heterocyclic aromatic amines (HAA) are representatives of carcinogenic and mutagenic compounds formed when muscle meat, including fish, is cooked, especially by frying and grilling. When these xenobiotic compounds enter the organism, they may be activated by metabolism into compounds with higher toxicity or carcinogenic potencial. Besides the enzymes of the phase I metabolism also the enzymes of the phase II metabolism mainly sulfotransferases (SULT) and N-acetyltransferases (NAT) may participate. Because these enzymes may be inducible their induction may be caused by other compounds present in food. Important inductors are some representatives of flavonoids - genistein, biochanin A and ß-naphtoflavone. These compounds have been proven to be able to to induce formation of sulfotransferases in vivo and in vitro conditions. An increased amount of enzymes may lead to the support of metabolic activation of procarcinogens, resulting in an increased formation of DNA aducts, causing development of carcinogenesis. For the research of induction of rat enzymes, rSULT and rNAT peptides were proposed that will be used for the production of antibodies suitable for their immunodetection.
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Study of cytochrome P450 intreaction with dietary carcinogens
Brabencová, Eliška ; Hodek, Petr (advisor) ; Burdová, Kamila (referee)
Humans are exposed to various carcinogens during their life. One of the main sources of carcinogens is a human diet which plays an important role in the cancer development. This bachelor thesis deals with carcinogens that are formed during a technological food processing or cooking of food - polycyclic aromatic hydrocarbons, heterocyclic amines and nitrosamines, then carcinogens produced by fungi - mycotoxins, and carcinogens that are produced by plants - safrole, estragole and pyrrolizidine alkaloids. Among numerous enzymes involved in metabolism of carcinogens, cytochromes P450 belong to the most important ones. These enzymes constitute a superfamily of haem-thiolate proteins, which is significantly involved in the metabolism of many foreign compounds (e.g. carcinogens, drugs, pollutants). Cytochromes P450 catalyze mainly reactions leading to detoxification of harmful compounds. Besides these reactions, the metabolic activation of compounds to more toxic products may occur. Cytochromes P450 play an important role in the activation of carcinogens to reactive electrophiles causing DNA damage. The subject of this bachelor thesis is to show mechanisms of metabolic activation of carcinogens. Key words: cytochromes P450, carcinogenesis, food carcinogens (In Czech)
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