engleski

Age related genotoxicity and mutagenesis studies

For decades it was believed that the differences in the level of adult and child genome damage caused by physical and chemical agents were basically rooted in different body mass neglecting the influence of developmental dynamics between birth and puberty. Projects and international campaigns launched over the last few years have started to accumulate data on time frames in which children express specific sensitivity to xenobiotics. The objective is to prepare legislation specifically adapted for children and their health protection. The Chernobyl tragedy has raised the issue on subpopulations of children who will have to deal with lifelong consequences of long term low dose exposure to ionizing radiation. Pharmaceutical and chemical industry have intensified their efforts to produce new animal models for evaluation and re-evaluation of pharmaceuticals which for the first time consider cytogenetic damage caused by intrauterine exposure or exposure in the first days of life. Applying available results from western literature and ex-Soviet countries, we launched an animal model for developmental genotoxicology testing and used it to re-evaluate pharmaceuticals which have been marketed for years, such as 5-nitrofurantoin, paracetamolum and fluconazole. In this animal model, 3 weeks and 8 weeks old mice are followed up for two week period using in vivo micronucleus assay. Blood samples from tail vein were taken before injection and 48h, 96h, 168h and 2 weeks after application. Significant age related difference in the level of genome damage caused by applied agents and the rate of its elimination was detected. For tested agents response peak was 48h after application. Future research should be focused on bioaccumulation of clastogenic and aneugenic agents during fetal development and childhood, on the influence of hormones on genotoxicological sensitivity of children, on the etiology of specific neoplasms in young population which may originate from specific childhood exposures and on the modeling of new test batteries for pediatric pharmacology.

genome damage; age; in vivo micronucleus

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