Chloroethylating anticancer drug-induced mutagenesis and its repair in Escherichia coli
Tóm tắt
Chloroethylnitrosourea (CENU) derivatives, such as nimustine (ACNU) and carmustine (BCNU), are employed in brain tumor chemotherapy due to their ability to cross the blood-brain barrier. They are thought to suppress tumor development through DNA chloroethylation, followed by the formation of interstrand cross-links (ICLs) that efficiently block replication and transcription. However, the alkylation of DNA and ICLs may trigger genotoxicity, leading to tumor formation as a side effect of the chemotherapeutic treatment. Although the involvement of O6-alkylguanine-DNA alkyltransferase (AGT) in repairing chloroethylated guanine (O6-chloroethylguanine) has been reported, the exact lesion responsible for the genotoxicity and the pathway responsible for repairing it remains unclear. We examined the mutations induced by ACNU and BCNU using a series of Escherichia coli strains, CC101 to CC111, in which reverse mutations due to each episome from F’101 to F’106 and frameshift mutations due to each episome from F’107 to F’111 could be detected. The mutant frequency increased in E. coli CC102, which can detect a GC to AT mutation. To determine the pathway responsible for repairing the CENU-induced lesions, we compared the frequency of mutations induced by CENU in the wild-type strain to those in the ada, ogt (AGT-deficient) strain, uvrA (nucleotide excision repair (NER)-deficient) strain, mismatch repair (MMR)-deficient strains, and recA (recombination deficient) strain of E. coli CC102. The frequencies of mutations induced by ACNU and BCNU increased in the ada, ogt strain, demonstrating that O6-chloroethylguanines were formed, and that a portion was repaired by AGT. Mutation induced by ACNU in NER-deficient strain showed a similar profile to that in AGT-deficient strain, suggesting that an NER and AGT play at the similar efficacy to protect E. coli from mutation induced by ACNU. O6-Chloroethylguanine is reported to form ICLs if it is not repaired. We examined the survival rates and the frequencies of mutations induced by ACNU and BCNU in the uvrA strain, the recA strain, as well as a double-deficient strain of CC102. The mutation profile of the double-deficient strain was similar to that of the NER-deficient strain, suggesting that an NER protects E. coli from mutations but not recombination. In addition, cell death was more pronounced in the uvrA, recA double-deficient strain than in the single-deficient strains. These results suggest that the toxic lesions induced by CENU were repaired additively or synergistically by NER and recombination. In other words, lesions, such as ICLs, appear to be repaired by NER and recombination independently.
Tài liệu tham khảo
Hurley LH. DNA and associated processes as targets for cancer therapy. Nat Rev Cancer. 2002;2:188–200.
Middleton MR, Margison GP. Improvement of chemotherapy efficacy by inactivation of a DNA-repair pathway. Lancet Oncol. 2003;4:37–44.
Fu D, Calvo JA, Samson LD. Balancing repair and tolerance of DNA damage caused by alkylating agents. Nat Rev Cancer. 2012;12:104–20.
Drabløs F, Feyzi E, Aas PA, Vaagbø CB, Kavli B, Bratlie MS, Peña-Diaz J, Otterlei M, Slupphaug G, Krokan HE. Alkylation damage in DNA and RNA--repair mechanisms and medical significance. DNA Repair (Amst). 2004;3:1389–407.
Nikolova T, Hennekes F, Bhatti A, Kaina B. Chloroethylnitrosourea-induced cell death and genotoxicity: cell cycle dependence and the role of DNA double-strand breaks. HR and NHEJ Cell Cycle. 2012;11:2606–19.
Nikolova T, Roos WP, Krämer OH, Strik HM, Kaina B. Chloroethylating nitrosoureas in cancer therapy: DNA damage, repair and cell death signaling. Biochim Biophys Acta. 2017;1868:29–39.
Wang Z, Sun H, Yakisich JS. Overcoming the blood-brain barrier for chemotherapy: limitations, challenges and rising problems. Anti Cancer Agents Med Chem. 2014;14:1085–93.
Liu HL, Hua MY, Chen PY, Chu PC, Pan CH, Yang HW, Huang CY, Wang JJ, Yen TC, Wei KC. Blood-brain barrier disruption with focused ultrasound enhances delivery of chemotherapeutic drugs for glioblastoma treatment. Radiology. 2010;255:415–25.
Swann PF. Why do O 6-alkylguanine and O 4-alkylthymine miscode? The relationship between the structure of DNA containing O 6-alkylguanine and O 4-alkylthymine and the mutagenic properties of these bases. Mutat Res. 1990;233:81–94.
Tong WP, Kirk MC, Ludlum DB. Formation of the cross-link 1-[N 3-deoxycytidyl], 2-[N 1-deoxyguanosinyl]ethane in DNA treated with N,N’-bis(2-chloroethyl)-N-nitrosourea. Cancer Res. 1982;42:3012–5.
Dronkert ML, Kanaar R. Repair of DNA interstrand cross-links. Mutat Res. 2001;486:217–47.
Ludlum DB. DNA alkylation by the haloethynitrosoureas: nature of modifications produced and their enzymatic repair or removal. Mutat Res. 1990;233:117–26.
Li L, Li S, Sun G, Peng R, Zhao L, Zhong R. Influence of the expression level of O 6-alkylguanine-DNA alkyltransferase on the formation of DNA interstrand crosslinks induced by chloroethylnitrosoureas in cells: a quantitation using high-performance liquid chromatography-mass spectrometry. PLoS One. 2015;10:e0121225.
Preuss I, Thust R, Kaina B. Protective effect of O 6-methylguanine-DNA methyltransferase (MGMT) on the cytotoxic and recombinogenic activity of different antineoplastic drugs. Int J Cancer. 1996;65:506–12.
Verbeek B, Southgate TD, Gilham DE, Margison GP. O 6-Methylguanine-DNA methyltransferase inactivation and chemotherapy. Br Med Bull. 2008;85:17–33.
Wiencke JK, Wiemels J. Genotoxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). Mutat Res. 1995;339:91–119.
Cupples CG, Miller JH. A set of lacZ mutations in Escherichia coli that allow rapid detection of each of the six base substitutions. Proc Natl Acad Sci U S A. 1989;86:5345–9.
Cupples CG, Cabrera M, Cruz C, Miller JH. A set of lacZ mutations in Escherichia coli that allow rapid detection of specific frameshift mutations. Genetics. 1990;125:275–80.
Negishi K, Loakes D, Schaaper RM. Saturation of DNA mismatch repair and error catastrophe by a base analogue in Escherichia coli. Genetics. 2002;161:1363–71.
Taira K, Kaneto S, Nakano K, Watanabe S, Takahashi E, Arimoto S, Okamoto K, Schaaper RM, Negishi K, Negishi T. Distinct pathways for repairing mutagenic lesions induced by methylating and ethylating agents. Mutagenesis. 2013;28:341–50.
Watanabe-Akanuma M, Ohta T. Effects of DNA repair deficiency on the mutational specificity in the lacZ gene of Escherichia coli. Mutat Res. 1994;311:295–304.
Takahashi E, Okamoto K, Arimoto S, Yamanaka H, Negishi T. Involvement of the drug efflux protein TolC in mutagenicity induced by MNNG or Trp-P-2. Mutat Res. 2006;605:42–50.
Taira K, Nakamura S, Nakano K, Maehara D, Okamoto K, Arimoto S, Loakes D, Worth L Jr, Schaaper RM, Seio K, Sekine M, Negihsi K, Negishi T. Binding of MutS protein to oligonucleotides containing a methylated or an ethylated guanine residue, and correlation with mutation frequency. Mutat Res. 2008;640:107–12.
Nakano K, Yamada Y, Takahashi E, Arimoto S, Okamoto K, Negishi K, Negishi T. E. coli mismatch repair enhances AT-to-GC mutagenesiss caused by alkylating agents. Mutat Res. 2017;815:22–7.
Rasmussen LJ, Samson L. The Escherichia coli MutS DNA mismatch binding protein specifically binds O 6-methylguanine DNA lesions. Carcinogenesis. 1996;17:2085–8.
Stojic L, Brun R, Jiricny J. Mismatch repair and DNA damage signalling. DNA Repair (Amst). 2004;3:1091–101.
Tashima M, Sawada H, Uchino H, Nishioka H. Effect of 1,3-bis (2-chloroehtyl)-29.-nitrosourea on Escherichia coli DNA repair system. Gan. 1978;69:695–8.
Sato K, Kitajima Y, Koga Y, Miyazaki K. The effect of O 6-methylguanine-DNA methyltransferase (MGMT) and mismatch repair gene (hMLH1) status on the sensitivity to alkylating agent 1-(4-amino-2-methyl-5-pyrimidinyl) methyl-3-(2-chloroethyl)-3-nitrosourea (ACNU) in gallbladder carcinoma cells. Anticancer Res. 2005;25:4021–8.
Suzuki M, Sugimoto Y, Tsuruo T. Efficient protection of cells from the genotoxicity of nitrosoureas by the retrovirus-mediated transfer of human O 6-methylguanine-DNA methyltransferase using bicistronic vectors with human multidrug resistance gene 1. Mutat Res. 1998;401:133–41.
Becker K, Gregel CM, Kaina B. The DNA repair protein O 6-methylguanine-DNA methyltransferase protects against skin tumor formation induced by antineoplastic chloroethylnitrosourea. Cancer Res. 1997;57:3335–8.
Mazon G, Philippin G, Cadet J, Gasparutto D, Fuchs RP. The alkyltransferase-like ybaZ gene product enhances nucleotide excision repair of O 6-alkylguanine adducts in E. coli. DNA Repair (Amst). 2009;8:697–703.
Mazon G, Philippin G, Cadet J, Gasparutto D, Modesti M, Fuchs RP. Alkyltransferase-like protein (eATL) prevents mismatch repair-mediated toxicity induced by O 6-alkylguanine adducts in Escherichia coli. Proc Natl Acad Sci U S A. 2010;107:18050–5.
Numata M, Hata H, Tohda H, Yasui A, Oikawa A. DNA repair pathways in mammalian cells analyzed by isolation of ACNU-sensitive Chinese hamster ovary cells. Tohoku J Exp Med. 1992;168:123–8.
He YH, Xu Y, Kobune M, Wu M, Kelley MR, Martin WJ 2nd. Escherichia coli FPG and human OGG1 reduce DNA damage and cytotoxicity by BCNU in human lung cells. Am J Physiol Lung Cell Mol Physiol. 2002;282:L50–5.
Pegg AE, Kanugula S, Loktionova NA. O 6-Alkylguanine-DNA alkyltransferase. In: Penning MT, editor. Chemical Carcinogenesis. Totowa: Humana Press; 2011. p. 321–43.
Bessho T. Induction of DNA replication-mediated double strand breaks by psoralen DNA interstrand cross-links. J Biol Chem. 2003;278:5250–4.
Sladek FM, Munn MM, Rupp WD, Howard-Flanders P. In vitro repair of psoralen-DNA cross-links by RecA, UvrABC, and the 5′-exonuclease of DNA polymerase I. J Biol Chem. 1989;264:6755–65.
Berardini M, Foster PL, Loechler EL. DNA polymerase II (polB) is involved in a new DNA repair pathway for DNA intastrand cross-links in Escherichia coli. J Bacteriol. 1999;181:2878–82.
Cole JM, Acott JD, Courcelle CT, Courcelle J. Limited capacity or involvement of excise on repair, double strand breaks, or translesion synthesis for psoralen cross-link repair in Eschericha coli. Genetics. 2018;210:99–112.
Pepponi R, Marra G, Fggetta MP, Falcinelli S, Pagani E, Bonmassar E, Jiricny J, D’Atri S. The effect of O 6-alkylguanine-DNA alkyltransferase and mismatch repair activities on the sensitivity of human melanoma cells to temozolomide, 1,3-bis(2-chloroethyl)1-nitrosourea, and cisplatin. J Pharacol Exp Ther. 2003;304:661–8.
Sanada M, Hidaka M, Takagi Y, Takano TY, Nakatsu Y, Tsuzuki T, Sekiguchi M. Modes of actions of two types of anti-neoplastic drugs, dacarbazine and ACNU, to induce apoptosis. Carcinogenesis. 2007;28:2657–26.