Chromosomal aberrations in subjects exposed to genotoxicants in cancer patients

0475636 - ÚEM 2018 RIV US eng C - Konferenční příspěvek (zahraniční konf.)
Vodička, Pavel - Polívková, Z. - Mušák, L. - Dušinská, M. - Vodenková, Soňa - Vymetálková, Veronika - Procházka, Pavel - Vodičková, Ludmila - Demová, H. - Poláková, Veronika - Ambruš, M. - Kumar, R. - Hemminki, K.
Chromosomal aberrations in subjects exposed to genotoxicants in cancer patients.
Proceedings of 3rd International Summit on Toxicology and Applied Pharmacology. Los Angeles: OMICS International, 2014.
[International Summit on Toxicology and Applied Pharmacology /3./. Chicago (US), 20.10.2014-22.10.2014]
Grant CEP: GA ČR(CZ) GAP304/12/1585; GA MZd(CZ) NT14329; GA MŠMT(CZ) LH13061
Institucionální podpora: RVO:68378041
Klíčová slova: chromosomal aberrations * single nucleotide polymorphisms * incident cancer patients * cancer risk * CIN
Obor OECD: Biochemistry and molecular biology

Human cancers often arise from cells unable to maintain genomic and chromosomal stability, mainly due to altered DNA repair mechanisms. Chromosomal instability (CIN) and alterations in the number of chromosomes are consistently observed in virtually all cancers. Non-specific chromosomal aberrations (CAs) may arise as a result of direct DNA damage by, for example, ionizing radiation or replication on a damaged DNA template. Non-specific CAs remain in lymphocytes for their lifetime. They have been used in monitoring of radiation exposure and exposure to genotoxic compounds and, together with sister chromatid exchanges and micronuclei. CAs poses the only available method for human biomonitoring for genotoxic exposures as well as estimation of tentative cancer risk. We assayed for chromosomal aberrations in 1028 healthy subjects, exposed to various potentially carcinogenic compounds and in 751 unexposed healthy subjects. We investigated CAs in association with polymorphisms of metabolizing enzymes, enzymes involved in regulation of cell cycle and cyclin D genotypes. Our data suggest biological basis for the link between CAs and cancer risk. Moreover we investigated chromosomal damage in lymphocytes of incident cancer patients (158 breast, 101 colorectal and 87 lung cancer patients) and compared to control groups. The study shows interesting elevation in chromosomal damage with the onset of cancer and this phenomenon merits further investigation.
Since CIN hallmarks nearly 65-70% of CRC tumors, we assayed for the CIN by aCGH in colon tumor tissues and healthy mucosa. Striking diference in CIN was observed between the right and left colon. Additionally, we analysed long deletions in CRC tumor suppresor gene MLH1.

Trvalý link: http://hdl.handle.net/11104/0272304