Abstract
The Ty1 assay is a short-term test for detection of genotoxins based on induction of the transposition of a gene-engineered Ty1 retrotransposon in Saccharomyces cerevisiae cells. Here, we provide evidence that the Ty1 test responds positively in concentration-dependent manner to the carcinogenic genotoxins benz(a)anthracene, benzo(a)pyrene, chenodeoxycholic and taurodeoxycholic free bile acids and to environmental soil samples polluted with carcinogenic substances. The Ty1 test gives negative results with the noncarcinogenic mutagens benz(b)anthracene, benzo(e)pyrene, lithocholic and taurodeoxycholic conjugated bile acids and to soil samples not polluted with carcinogens. Presence or absence of genotoxins in soil samples was evidenced by chemical analysis. Several explanations for the sensitive differential test’s response to genotoxins are proposed and discussed. It is concluded that the Ty1 test can complement existing assays in laboratory and environmental studies showing high sensitivity to a wider spectrum of carcinogenic genotoxins.
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Alder ID, Parry JM (1993) Development of screening tests for aneuploidy induction by environmental pollutants. Environ Health Perspect 101:5–9
Ashby J, Tennant R, Definite W (1991) Defined relationship among chemical structure, carcinogenicity and mutagenicity for 301 chemicals tested by the U.S. NTP. Mutat Res 275:229–306
Bartsch H, Mallaveille C, Camus AM, Martel-Planche G, Brun G, Hautefuelle A, Sabadie N, Barbin A, Kuroki T, Drevon C, Piccoli C, Montesano R (1980) Validation and comparative studies on 180 chemicals with S. typhimurium strains and V79 Chinese hamster cells in the presence of various metabolizing systems. Mutat Res 76:1–50
Bernstein H, Bernstein C, Payne CM, Dvorakova K, Garawel H, (2005) Bile acids as carcinogens in human gastrointestinal cancers. Mutat Res 589:87–93
Bertram JS (2001) The molecular biology of cancer. Mol Aspects Med 21:167–223
Chang RL, Levin W, Word AW, Lekr RE, Kumar S, Yagi H, Jerina DM, Conney AH (1981) Tumorogenicity of the diasteromeric bay-region benzo(e)pyrene 9,10-diol-11,12-expodes in newborn mice. Cancer Res 41:915–918
Curcio MJ, Garfinkel DJ (1999) New lines of host defense: inhibition of Ty1 retrotransposition by Fus 3p and NER/TFII H. Trends Genet 15:43–45
Drake JW (1998) The molecular bases of mutation. Holden Day, Oakland, p 382
Garfinkel DJ (1992) Retroelements in microorganisms. In: Levy JA (ed) Retroviridae. Plenum Press, New York, pp 107–163
Garfinkel DJ (2005) Genome evolution mediated by Ty elements in Saccharomyces. Cytogenet Genome Res 110:63–69
Goldman R, Enwold L, Pellizzari E, Beach G, Bowman E, Krishnan S, Shields P (2001) Smoking increases carcinogenic polycyclic aromatic hydrocarbons in human lung tissue. Cancer Res 61:6064–6371
Jurek D, Fleckl E, Marian B (2005) Bile acid induced gene expression in LT97 colonic adenoma cells. Food Chem Toxicol 43:87–93
Kirpnick Z, Homiski M, Rubitski E, Repnevskaya M, Howlett N, Aubrecht J, Schiestl RH (2005) Yeast DEL assay detect clastogens. Mutat Res 582:116–134
Kirsch-Volders M, Fenech M (2001) Induction of micronuclei in non-dividing mononuclear lymphocytes and necrosis/apoptosis may provide a more comprehensive cytokinesis block micronucleous assay for biomonitoring purposes. Mutagenesis 16:51–58
Lerry T, Hummelen van P, Anard D, Castelian P, Kirsh-Volders M, Lamveris R, Lison D (1996) Evaluation of three methods for the detection of DNA single-stranded breaks in human lymphocytes. J Toxicol Environ Health 47:409–442
Looby E, Long A, Kelleher D, Velkov Y (2005) Bile acid deoxycholate induces differential subcellular localization of the PKC isoenzymes beta1, epsilon and delta in colonic epithelial cells in a sodium butyrate insensitive manner. Int J Cancer 144:887–895
Maron DM, Ames B (1983) Revised methods for the Salmonella mutagenicity test. Mutat Res 113:173–215
Morita T, Iwamoto Y, Shimizu T, Maswazawa T, Yanagihara Y (1989) Mutagenicity test with a permeable mutant of yeast on carcinogens showing false negative Salmonella assay. Chem Pharm Bull 37:407–409
Parry JM, Shamsher M, Skibinski DO (1990) Restriction site mutation analysis, a proposed methodology for the detection and study of DNA base changes following mutagen exposure. Mutagenesis 5:209–212
Perera F, Tang D, Whyatt R, Lederman W, Jedrychowski W (2005) DNA damage from polycyclic aromatic hydrocarbons measured by benzo(a)pyrene-DNA adduct in mother and newborn from Northeon Manhatten, the Word Trade Center Area, Poland and China. Cancer Epidemiol Biomarkers Prev 14:709–714
Pesheva M, Krastanova O, Staleva L, Dentcheva V, Hadzhitodorov M, Venkov P (2005) The Ty1 transposition test: a new short-term test for detection of carcinogens. J Microbiol Methods 61:1–8
Ramel C, Cederberg H, Magmusson J, Vogel E, Natarajen AT, Mullander LH, Nivard JM, Parry JM, Leyson A, Comendator MA, Siera LM Ferreiro JA, Consuegra S (1996) Somatic recombination gene amplification and cancer. Mutat Res 353:85–107
Rossi C, Poli P, Buschini A, Cassoni F, Galli A, Vellosi R, Carratore R (1991) Genetic activity of samples collected from a waste incinerator and its neighboring areas. Toxic Environ Chem 30:51–61
Salamone MF (1981) Toxicity of 41 carcinogens and noncarcinogenic analogs. Prog Mutat Res 1:682–685
Schiestl RH, Geitz RD, Mehta RD, Hastings PJ (1989) Carcinogens induce intrachromosomal recombination in yeast. Carcinogenesis 10:1445–1455
Seike K, Murate M, Harakawa K, Deyashiky Y, Kawanaishi S (2004) Oxidative DNA damage induced by benz(a)anthracene dihydrodiols in the presence of dihydrodioldehydrogenase. Chem Res Toxicol 17:1445–1451
Sherman F, Fink GR, Hicks R (1996) Laboratory course manual for methods in yeast genetics. Cold Spring Harbor Laboratory Press, New York
Staleva L, Walcheva L, Venkov P (1996) Enchanced permeability increases the sensitivity of a yeast test for mutagens. Mutat Res 370:81–89
Staleva LS, Venkov PV (2001) Activation of Ty1 transposition by mutagens. Mutat Res 474:93–103
Stoycheva T, Massarado DR, Pesheva M, Venkov P, Wolf K, Giudice LD, Pontieri P (2007) Ty1 transposition induced by carcinogens in S. cerevisiae yeast depends on mitochondrial function. Gene 389:212–218
Verschueren E (2001) Handbook at Environmental Data on Organic Chemicals, 4th edn, vol 1. Wiley, New York, pp 1158–1161
Zimmerman FK, Kern R, Rassenberg H (1975) A yeast strain for simultaneous detection of induced mitotic crossingover, mitotic gene conversion and reverse mutation. Mutat Res 28:381–338
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This research was supported partially by grant NATO SfP 977977 given to P.V.
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Pesheva, M., Krastanova, O., Stamenova, R. et al. The response of Ty1 test to genotoxins. Arch Toxicol 82, 779–785 (2008). https://doi.org/10.1007/s00204-008-0299-5
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DOI: https://doi.org/10.1007/s00204-008-0299-5