Tolerance to O6-Methylguanine and 6-Thioguanine Cytotoxic Effects: A Cross-resistant Phenotype in N-Methylnitrosourea-resistant Chinese Hamster Ovary Cells

作者: E. Dogliotti , A. Zijno , A. Di Muccio , G. Aquilina , A. M. Giammarioli

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摘要: The biochemical and genetic characteristics of a clone Chinese hamster ovary cells displaying resistance to N-methyl-N-nitrosourea (MNU) 6-thioguanine (6-TG) were analyzed. initial level 7-methylguanine, 3-methyladenine, O6-methylguanine formation the repair rates for these alkylated bases same in resistant parental cell line, indicating that alkylation damage is not due differences DNA alkylation. After exposure 24 or 48 h 6-TG (0.6 micrograms/ml) culture medium, contrast them, was able replicate containing base analogue during following h. These data are agreement with hypothesis tolerate both present DNA. tolerance MNU also included chromosomal induced by two agents, MNU-resistant incurred less sister chromatid exchanges after treatment either 6-TG. 6-TG-resistant cells, selected growth 6-TG, exhibited cross-resistance but methyl methanesulfonate, confirming common pathway responsible O6-methylguanine.

参考文章(30)
S. C. Barranco, R. M. Humphrey, The effects of beta-2'-deoxythioguanosine on survival and progression in mammalian cells. Cancer Research. ,vol. 31, pp. 583- 586 ,(1971)
J. Maybaum, A. N. Bainnson, J. J. Kroll, L. M. Iwaniec, W. M. Roethel, D. R. Terbush, Sudhir Ajmera, Effects of incorporation of 6-thioguanine into SV40 DNA Molecular Pharmacology. ,vol. 32, pp. 606- 614 ,(1987)
H. George Mandel, Jonathan Maybaum, Unilateral chromatid damage: a new basis for 6-thioguanine cytotoxicity. Cancer Research. ,vol. 43, pp. 3852- 3856 ,(1983)
Alan R. P. Paterson, David M. Tidd, A biochemical mechanism for the delayed cytotoxic reaction of 6-mercaptopurine. Cancer Research. ,vol. 34, pp. 738- 746 ,(1974)
D. B. Ellis, G. A. LePage, Biochemical Studies of Resistance to 6-Thioguanine Cancer Research. ,vol. 23, pp. 436- 443 ,(1963)
R Ding, K Ghosh, A Eastman, E Bresnick, DNA-mediated transfer and expression of a human DNA repair gene that demethylates O6-methylguanine. Molecular and Cellular Biology. ,vol. 5, pp. 3293- 3296 ,(1985) , 10.1128/MCB.5.11.3293
M. Bignami, M. Terlizzese, A. Zijno, A. Calcagnile, G. Frosina, A. Abbondandolo, E. Dogliotti, Cytotoxicity, mutations and SCEs induced by methylating agents are reduced in CHO cells expressing an active mammalian O6-methylguanine-DNA methyltransferase gene Carcinogenesis. ,vol. 8, pp. 1417- 1421 ,(1987) , 10.1093/CARCIN/8.10.1417