caa a22 4500 445852585 CHVBK 20180317145417.0 cr unu---uuuuu 170323e20110101xx s 000 0 eng 10.1007/s00204-010-0542-8 doi (NATIONALLICENCE)springer-10.1007/s00204-010-0542-8 The positive response of Ty1 retrotransposition test to carcinogens is due to increased levels of reactive oxygen species generated by the genotoxins [Elektronische Daten] [Martin Dimitrov, Pencho Venkov, Margarita Pesheva] In previous laboratory and environmental studies, the Ty1 short-term test showed positive responses (i.e. induced mobility of the Ty1 retrotransposon) to carcinogenic genotoxins. Here, we provide evidence for a causal relationship between increased level of reactive oxygen species and induction the mobility of the Ty1 retrotransposon. Results obtained in concentration and time-dependent experiments after treatment, the tester cells with carcinogenic genotoxins [benzo(a)pyrene, benzo(a)anthracene, ethylmethanesulfonate, formamide], free bile acids (chenodeoxycholic, lithocholic acids) and metals (arsenic, hexavelant chromium, lead) showed a simultaneous increase in both cellular level of the superoxide anions and Ty1 retrotransposition rates. Treatment with the noncarcinogenic genotoxins [benzo(e)pyrene, benzo(b)anthracen, anthracene], conjugated bile acids (taurodeoxycholic, glycodeoxycholic acids) and metals (zinc, trivalent chromium) did not change significantly superoxide anions level and Ty1 retrotransposition rate. The induction by carcinogens of the Ty1 mobility seems to depend on the accumulation of superoxide anions, since the addition of the scavenger N-acetylcysteine resulted in loss of both increased amount of superoxide anions and induced Ty1 retrotransposition. Increased hydrogen peroxide levels are also involved in the induction of Ty1 retrotransposition rates in response to treatment with carcinogenic genotoxins, as evidenced by disruption of YAP1 gene in the tester cells. It is concluded that the carcinogen-induced high level of reactive oxygen species play a primary and key role in determination the selective response of Ty1 test to carcinogenic genotoxins. Springer-Verlag, 2010 Ty1 retrotransposition nationallicence Carcinogens nationallicence Reactive oxygen species nationallicence Dimitrov Martin Sofia University Faculty of Biology, 8 "Dragan Tsankov” blvd, 1421, Sofia, Bulgaria aut Venkov Pencho Institute of Cryobiology and Food Technology, 53A "Cherni Vrah” blvd, 1407, Sofia, Bulgaria aut Pesheva Margarita Sofia University Faculty of Biology, 8 "Dragan Tsankov” blvd, 1421, Sofia, Bulgaria aut Archives of Toxicology Springer-Verlag 85/1(2011-01-01), 67-74 0340-5761 85:1<67 2011 85 204 https://doi.org/10.1007/s00204-010-0542-8 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00204-010-0542-8 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Dimitrov Martin Sofia University Faculty of Biology, 8 "Dragan Tsankov” blvd, 1421, Sofia, Bulgaria aut NATIONALLICENCE 700 1- Venkov Pencho Institute of Cryobiology and Food Technology, 53A "Cherni Vrah” blvd, 1407, Sofia, Bulgaria aut NATIONALLICENCE 700 1- Pesheva Margarita Sofia University Faculty of Biology, 8 "Dragan Tsankov” blvd, 1421, Sofia, Bulgaria aut NATIONALLICENCE 773 0- Archives of Toxicology Springer-Verlag 85/1(2011-01-01), 67-74 0340-5761 85:1<67 2011 85 204 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer