Application of UV-Induced Unscheduled DNA-Synthesis Measurements in Human Genotoxicological Risk Assessment

摘要: Cancer development is a long-term, multistep process with complex interplay between genes and environment. The magnitude of environmental effects depends on the presence or absence genetic susceptibility subjects to certain cancer types. Molecular epidemiological studies in have proved, that besides target cell instability, triggering exposure critical [Albertini & Hayes 1997, Newby &Howard 2005]. biomarker responses, character route different factors (chemicals, physical agents biological agents) are also important causing tumors especially cases occupational [Ward 1995]. EPA Guidelines for carcinogen Risk Assessment [EPA 2005] based mode action chemicals, such as interaction DNA, cytotoxicity, binding receptors modifying signal pathways. There several natural compounds – so called chemopreventive agents- which able modify genotoxic mutagenic response (Ames 1983) organisms. These vitamins, antioxidants, phytochemicals, micro nutrients available market without knowing their action. Mutagenesis caused by chemicals can be prevented protection cell’s DNA replication, increasing repair capacity delaying replication allow enough time make complete damaged cells.  Antioxidants protect cells from oxidative stress, stimulate phase I reactions including oxidation, reduction, hydrolysis xenobiotics monoxigenase detoxicating key enzymes, CYP450 [Xu et al.1996, Poulsen &Loft]. changes increase polarity these molecules help conjugate them II glucuronic acid, acetic acid sulfuric physiological ways eliminate active metabolites cells. best studied crucial early event carcinogenesis chromosomal aberration, microsatellite abnormal number chromosomes (aneuploidy), gene amplification loss heterozygosity tumor suppressor genes. By reducing mutation via chemoprevention, may survive any permanent damage, it go through pathway apoptosis, occurring P53 [Lowe&Lin 2000].