Methotrexate-induced cytotoxicity and genotoxicity in germ cells of mice: Intervention of folic and folinic acid

Mutation Research - Genetic Toxicology and Environmental Mutagenesis

Volumn 673, Issue 1, 2009, Pages 43-52

  Padmanabhan, S ^a   Tripathi, D N ^a   Vikram, A ^a   Ramarao, P ^a   Jena, G B ^a  

^a NATIONAL INSTITUTE OF PHARMACEUTICAL EDUCATION AND RESEARCH NIPER   (India)

Author keywords

Folic acid; Folinic acid; Methotrexate; Mice; Sperm; Testis

Indexed keywords

FOLIC ACID; FOLINIC ACID; METHOTREXATE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CELL PROTECTION; COMET ASSAY; CONTROLLED STUDY; CYTOTOXICITY; DNA DAMAGE; GENOTOXICITY; GERM CELL; MALE; NICK END LABELING; NONHUMAN; PRIORITY JOURNAL; SEMEN ABNORMALITY; SEMINIFEROUS TUBULE EPITHELIUM; SPERMATOZOON; SPERMATOZOON COUNT; SWISS WEBSTER MOUSE; TESTIS WEIGHT; THERAPY EFFECT; TISSUE SECTION; TREATMENT DURATION; TREATMENT OUTCOME; TREATMENT RESPONSE;

ANIMALS; FOLIC ACID; GERM CELLS; IN SITU NICK-END LABELING; LEUCOVORIN; MALE; METHOTREXATE; MICE; MICROSCOPY; MOLECULAR STRUCTURE; SPERMATOZOA; TESTIS;

ANIMALIA; MUS;

EID: 58649093951     PISSN: 13835718     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mrgentox.2008.11.011     Document Type: Article

References (79)

1. Peters G.J., van der Wilt C.L., van Moorsel C.J., Kroep J.R., Bergman A.M., and Ackland S.P. Basis for effective combination cancer chemotherapy with antimetabolites. Pharmacol. Ther. 87 (2000) 227-253
2. Choudhury R.C., Ghosh S.K., and Palo A.K. Cytogenetic toxicity of methotrexate in mouse bone marrow. Environ. Toxicol. Pharmacol. 8 (2000) 191-196
3. Miyazaki J., Kawai K., Hayashi H., Onozawa M., Tsukamoto S., Miyanaga N., Hinotsu S., Shimazui T., and Akaza H. The limited efficacy of methotrexate, actinomycin D and cisplatin (MAP) for patients with advanced testicular cancer. Jpn. J. Clin. Oncol. 33 (2003) 391-395
4. Seigers R., Schagen S.B., Beerling W., Boogerd W., van Tellingen O., van Dam F.S.A.M., Koolhaas J.M., and Buwalda B. Long-lasting suppression of hippocampal cell proliferation and impaired cognitive performance by methotrexate in the rat. Behav. Brain Res. 186 (2008) 168-175
5. Veronesi U., Bonadonna G., and Valagussa P. Lessons from the initial adjuvant cyclophosphamide, methotrexate, and fluorouracil studies in operable breast cancer. J. Clin. Oncol. 26 (2008) 342-344
6. Jensen S.B., Mouridsen H.T., Reibel J., Brunner N., and Nauntofte B. Adjuvant chemotherapy in breast cancer patients induces temporary salivary gland hypofunction. Oral Oncol. 44 (2008) 162-173
7. Liu R., Chang S.M., and Prados M. Recent advances in the treatment of central nervous system tumours. Update Cancer Ther. 3 (2008) 49-79
8. Novak K., and Swain M.G. Role of methotrexate in the treatment of chronic cholestatic disorders. Clin. Liver Dis. 12 (2008) 81-96
9. Choudhury R.C., and Palo A.K. Modulatory effects of caffeine on methotrexate-induced cytogenotoxicity in mouse bone marrow. Environ. Toxicol. Pharmacol. 15 (2004) 79-85
10. Kasahara Y., Nakai Y., Miura D., Yagi K., Hirabayashi K., and Makita T. Mechanism of induction of micronuclei and chromosome aberrations in mouse bone marrow by multiple treatments of methotrexate. Mutat. Res. 280 (1992) 117-128
11. Kasahara Y., Wakata A., Nakai Y., Yuno K., Miura D., Yagi K., Hirabayashi K., and Makita T. The micronucleus test using peripheral blood reticulocytes from methotrexate-treated mice. Mutat. Res. 278 (1992) 145-151
12. Zuniga-Gonzalez G.M., Gomez-Meda B.C., Zamora-Perez A.L., Ramos-Ibarra M.L., Batista-Gonzalez C.M., Lemus-Varela M.L., Rodriguez-Avila J.L., and Gallegos-Arreola M.P. Micronucleated erythrocyte frequencies in old and new world primates: measurement of micronucleated erythrocyte frequencies in peripheral blood of Callithrix jacchus as a model for evaluating genotoxicity in primates. Environ. Mol. Mutagen. 46 (2005) 253-259
13. Le Fevre A.C., Boitier E., Marchandeau J.P., Sarasin A., and Thybaud V. Characterization of DNA reactive and non-DNA reactive anticancer drugs by gene expression profiling. Mutat. Res. 619 (2007) 16-29
14. Graf U., Wurgler F.E., Katz A.J., Frei H., Juon H., Hall C.B., and Kale P.G. Somatic mutation and recombination test in Drosophila melanogaster. Environ. Mutagen. 6 (1984) 153-188
15. Wurgler F.E., Graf U., Frei H., and Juon H. Genotoxic activity of the anti-cancer drug methotrexate in somatic cells of Drosophila melanogaster. Mutat. Res. 122 (1983) 321-328
16. Kirpnick Z., Homiski M., Rubitski E., Repnevskaya M., Howlett N., Aubrecht J., and Schiestl R.H. Yeast DEL assay detects clastogens. Mutat. Res. 582 (2005) 116-134
17. Torous D.K., Hall N.E., Illi-Love A.H., Diehl M.S., Cederbrant K., Sandelin K., Ponten I., Bolcsfoldi G., Ferguson L.R., Pearson A., Majeska J.B., Tarca J.P., Hynes G.M., Lynch A.M., McNamee J.P., Bellier P.V., Parenteau M., Blakey D., Bayley J., van der Leede B.J., Vanparys P., Harbach P.R., Zhao S., Filipunas A.L., Johnson C.W., Tometsko C.R., and Dertinger S.D. Interlaboratory validation of a CD71-based flow cytometric method (Microflow) for the scoring of micronucleated reticulocytes in mouse peripheral blood. Environ. Mol. Mutagen. 45 (2005) 44-55
18. Barclay B.J., DeHaan C.L., Hennig U.G., Iavorovska O., von Borstel R.W., and von Borstel R.C. A rapid assay for mitochondrial DNA damage and respiratory chain inhibition in the yeast Saccharomyces cerevisiae. Environ. Mol. Mutagen. 38 (2001) 153-158
19. Maskaleris T., Lialiaris T., and Triantaphyllidis C. Induction of cytogenetic damage in human lymphocytes in vitro and of antineoplastic effects in Ehrlich ascites tumor cells in vivo treated by methotrexate, hyperthermia and/or caffeine. Mutat. Res. 422 (1998) 229-236
20. Amacher D.E., Paillet S., and Ray V.A. Point mutations at the thymidine kinase locus in L5178Y mouse lymphoma cells. I. Application to genetic toxicological testing. Mutat. Res. 64 (1979) 391-406
21. Chow M., Koo J., Ng P., and Rubin H. Random population-wide genetic damage induced in replicating cells treated with methotrexate. Mutat. Res. 413 (1998) 251-264
22. Brumen V., and Horvat D. Work environment influence on cytostatics-induced genotoxicity in oncologic nurses. Am. J. Ind. Med. 30 (1996) 67-71
23. Ramos-Remus C., Dorazco-Barragan G., Aceves-Avila F.J., Alcaraz-Lopez F., Fuentes-Ramirez F., Michel-Diaz J., Torres-Bugarin O., Ventura-Aguilar A., and Zuniga-Gonzalez G. Genotoxicity assessment using micronuclei assay in rheumatoid arthritis patients. Clin. Exp. Rheumatol. 20 (2002) 208-212
24. Lindskov R., Wulf H.C., Wantzin G.L., and Niebuhr E. Sister chromatid exchange in patients treated with methotrexate for psoriasis. J. Invest. Dermatol. 82 (1984) 458-459
25. Choudhury R.C., Ghosh S.K., and Palo A.K. Potential transmission of the cytogenetic toxic effects of methotrexate in the male germline cells of Swiss mice. Environ. Toxicol. Pharmacol. 10 (2001) 81-88
26. Padmanabhan S., Tripathi D.N., Vikram A., Ramarao P., and Jena G.B. Cytotoxic and genotoxic effects of methotrexate in germ cells of male swiss mice. Mutat. Res. 655 (2008) 59-67
27. Canistro D., Pozzetti L., Sapone A., Broccoli M., Bonamassa B., Longo V., Lubrano V., Barillari J., Biagi G.L., and Paolini M. Perturbation of rat hepatic metabolising enzymes by folic acid supplementation. Mutat. Res. 637 (2008) 16-22
28. Jennings E. Folic acid as a cancer-preventing agent. Med. Hypotheses 45 (1995) 297-303
29. Ames B.N. DNA damage from micronutrient deficiencies is likely to be a major cause of cancer. Mutat. Res. 475 (2001) 7-20
30. 12 against chromosome damage induced by manganese sulfate in cultured mouse spleen cells. Cytologia 67 (2002) 221-228
31. Dijkmans B.A. Folate supplementation and methotrexate. Br. J. Rheumatol. 34 (1995) 1172-1174
32. Harten P. Reducing toxicity of methotrexate with folic acid. Z. Rheumatol. 64 (2005) 353-358
33. Ortiz Z., Shea B., Suarez Almazor M., Moher D., Wells G., and Tugwell P. Folic acid and folinic acid for reducing side effects in patients receiving methotrexate for rheumatoid arthritis. Cochrane Database Syst. Rev. (2000) CD000951
34. Morgan S.L., Baggott J.E., Lee J.Y., and Alarcon G.S. Folic acid supplementation prevents deficient blood folate levels and hyperhomocysteinemia during longterm, low dose methotrexate therapy for rheumatoid arthritis: implications for cardiovascular disease prevention. J. Rheumatol. 25 (1998) 441-446
35. Schilsky R.L. Methotrexate: an effective agent for treating cancer and building careers. The Polyglutamate Era. Stem Cells 14 (1996) 29-32
36. McLeod H.L. Clinically elevant drug-drug interactions in oncology. Br. J. Clin. Pharmacol. 45 (1998) 539-544
37. Comella P. A review of the role of capecitabine in the treatment of colorectal cancer. Ther. Clin. Risk Manage. 3 (2007) 421-431
38. Raghunathan K., and Priest D.G. Modulation of fluorouracil antitumor activity by folic acid in a murine model system. Biochem. Pharmacol. 58 (1999) 835-839
39. Klein P., and Muggia F.M. Cytoprotection: shelter from the storm. Oncologist 4 (1999) 112-121
40. Links M., and Lewis C. Chemoprotectants-a review of their clinical pharmacology and therapeutic efficacy. Drugs 57 (1999) 293-308
41. Shahin A.A., Ismail M.M., Saleh A.M., Moustafa H.A., Aboul-Ella A.A., and Gabr H.M. Protective effect of folinic acid on low-dose methotrexate genotoxicity. Z. Rheumatol. 60 (2001) 63-68
42. Brown C.D., Forman C.L., McEuen S.F., and Miller M.G. Metabolism and testicular toxicity of 1,3-dinitrobenzene in rats of different ages. Fundam. Appl. Toxicol. 23 (1994) 439-446
43. Kishikawa H., Tateno H., and Yanagimachi R. Chromosome analysis of BALB/c mouse spermatozoa with normal and abnormal head morphology. Biol. Reprod. 61 (1999) 809-812
44. Wyrobek A.J., and Bruce W.R. Chemical induction of sperm abnormalities in mice. Proc. Natl. Acad. Sci. 72 (1975) 4425-4429
45. Vikram A., Tripathi D.N., Ramarao P., and Jena G.B. Intervention of d-glucose ameliorates the toxicity of streptozotocin in accessory sex organs of rat. Toxicol. Appl. Pharmacol. 226 (2008) 84-93
46. Cortazar I.C., Garcia M., Quiroga J., Diez N., Caballer F.D., Calvo A., Diaz M., and Prieto J. Insulin-like growth factor-I reverts testicular atrophy in rats with advanced cirrhosis. Hepatology 31 (2003) 592-600
47. Haines G.A., Hendry J.H., Daniel C.P., and Morris I.D. Germ cell and dose-dependent DNA damage measured by the comet assay in murine spermatozoaa after testicular X-irradiation. Biol. Reprod. 67 (2002) 854-861
48. Vikram A., Tripathi D.N., Ramarao P., and Jena G.B. Evaluation of streptozotocin genotoxicity in rats from different ages using the micronucleus assay. Regul. Toxicol. Pharmacol. 49 (2007) 238-244
49. Olive P.L. DNA damage and repair in individual cells: applications of the comet assay in radiobiology. Int. J. Radiat. Biol. 75 (1999) 395-405
50. Singh N.P. A simple method for accurate estimation of apoptotic cells. Exp. Cell Res. 256 (2000) 328-337
51. Sestili P., Martinelli C., and Stocchi V. The fast halo assay: an improved method to quantify genomic DNA strand breakage at the single-cell level. Mutat. Res. 607 (2006) 205-214
52. Chiang H.M., Fang S.H., Wen K.C., Hsiu S.L., Tsai S.Y., Hou Y.C., Chi Y.C., and Chao P.D. Life-threatening interaction between the root extract of Pueraria lobata and methotrexate in rats. Toxicol. Appl. Pharmacol. 209 (2005) 263-268
53. Uzar E., Koyuncuoglu H.R., Uz E., Yilmaz H.R., Kutluhan S., Kilbas S., and Gultekin F. The activities of antioxidant enzymes and the level of malondialdehyde in cerebellum of rats subjected to methotrexate: protective effect of caffeic acid phenethyl ester. Mol. Cell. Biochem. 291 (2006) 63-68
54. Aggarwal P., Naik S., Mishra K.P., Aggarwal A., and Misra R. Correlation between methotrexate efficacy & toxicity with C677T polymorphism of the methylenetetrahydrofolate gene in rheumatoid arthritis patients on folate supplementation. Indian J. Med. Res. 124 (2006) 521-526
55. Vinson R.K., and Hales B.F. Expression and activity of the DNA repair enzyme uracil DNA glycoslyase during organogenesis in the rat conceptus and following methotrexate exposure in vitro. Biochem. Pharmacol. 64 (2002) 711-721
56. Branda R.F., O'Neill J.P., Brooks E.M., Trombley L.M., and Nicklas J.A. The effect of folate deficiency on the cytotoxic and mutagenic responses to ethyl methanesulfonate in human lymphoblastoid cell lines that differ in p53 status. Mutat. Res. 473 (2001) 51-71
57. Knock E., Deng L., Wu Q., Lawrance A.K., Wang X.L., and Rozen R. Strain differences in mice highlight the role of DNA damage in neoplasia induced by low dietary folate. J. Nutr. 138 (2008) 653-658
58. Kapiszewska M., Kalemba M., Wojciech U., and Milewicz T. Uracil misincorporation into DNA of leukocytes of young women with positive folate balance depends on plasma vitamin B12 concentrations and methylenetetrahydrofolate reductase polymorphisms. A pilot study. J. Nutr. Biochem. 16 (2005) 467-478
59. Branda R.F., O'Neill J.P., Brooks E.M., Powden C., Naud S.J., and Nicklas J.A. The effect of dietary folic acid deficiency on the cytotoxic and mutagenic responses to methyl methanesulfonate in wild-type and in 3-methyladenine DNA glycosylase-deficient Aag null mice. Mutat. Res. 615 (2007) 12-17
60. Tian H., and Cronstein B.N. Understanding the mechanisms of action of methotrexate. Bull. NYU Hosp. Joint Dis. 65 (2007) 168-173
61. Selvakumar K.J., Hanneman W.H., and Schimenti J.C. Evidence for cyclophosphamide-induced gene conversion and mutation in mouse germ cells. Toxicol. Appl. Pharmacol. 147 (1997) 343-350
62. Aziz A.H.A., Shouman S.A., Attia A.S., and Saad S.F. A study on the reproductive toxicity of erythrosine in male mice. Pharmacol. Res. 35 (1997) 457-462
63. Fenech M. Micronutrients and genomic stability: a new paradigm for recommended dietary allowances (RDAs). Food Chem. Toxicol. 40 (2002) 1113-1117
64. Fenech M. Biomarkers of genetic damage for cancer epidemiology. Toxicology 181-182 (2002) 411-416
65. Zijno A., Andreoli C., Leopardi P., Marcon F., Rossi S., Caiola S., Verdina A., Galati R., Cafolla A., and Crebelli R. Folate status, metabolic genotype, and biomarkers of genotoxicity in healthy subjects. Carcinogenesis 24 (2003) 1097-1103
66. Wang X., Thomas P., Xue J., and Fenech M. Folate deficiency induces aneuploidy in human lymphocytes in vitro-evidence using cytokinesis-blocked cells and probes specific for chromosomes 17 and 21. Mutat. Res. 551 (2004) 167-180
67. Duthie S.J. Folic acid deficiency and cancer: mechanisms of DNA instability. Br. Med. Bull. 55 (1999) 578-592
68. Morgan S.L., Baggott J.E., and Alarcon G.S. Methotrexate in rheumatoid arthritis: folate supplementation should always be given. BioDrugs 8 (1997) 164-175
69. Ravelli A., Migliavacca D., Viola S., Ruperto N., Pistorio A., and Martini A. Efficacy of folinic acid in reducing methotrexate toxicity in juvenile idiopathic arthritis. Clin. Exp. Rheumatol. 17 (1999) 625-627
70. Srisomboon J., Suprasert P., Phongnarisorn C., Charoenkwan K., Siriaree S., Cheewakriangkrai C., Tantipalakorn C., and Kietpeerakool C. Treatment results of methotrexate and folinic acid as primary chemotherapy for nonmetastatic gestational trophoblastic neoplasia. J. Med. Assoc. Thai. 88 (2005) 886-890
71. Keshava C., Keshava N., Whong W.Z., Nath J., and Ong T.M. Inhibition of methotrexate-induced chromosomal damage by folinic acid in V79 cells. Mutat. Res. 397 (1998) 221-228
72. van der Veer L.J., Westerhof G.R., Rijksen G., Schornagel J.H., and Jansen G. Cytotoxicity of methotrexate and trimetrexate and its reversal by folinic acid in human leukemic CCRF-CEM cells with carrier-mediated and receptor-mediated folate uptake. Leuk. Res. 13 (1989) 981-987
73. Reidy J.A., Zhou X., and Chen A.T. Folic acid and chromosome breakage: implications for genotoxicity studies. Mutat. Res. 122 (1983) 217-221
74. Fenech M. Recommended dietary allowances (RDAs) for genomic stability. Mutat. Res. 480-481 (2001) 51-54
75. Yousef M.I., Demerdash F.M., Kamil K.I., and Elaswad F.A.M. Ameliorating effect of folic acid on chromium(VI)-induced changes in reproductive performance and seminal plasma biochemistry in male rabbits. Reprod. Toxicol. 21 (2006) 322-328
76. Li J., and Kaminskas E. Accumulation of DNA strand breaks and methotrexate cytotoxicity. Proc. Natl. Acad. Sci. 81 (1984) 5694-5698
77. Curtin N.J., Harris A.L., and Aherne G.W. Mechanism of cell death following thymidylate synthase inhibition: 2′-deoxyuridine-5′-triphosphate accumulation, DNA damage, and growth inhibition following exposure to CB3717 and dipyridamole. Cancer Res. 51 (1991) 2346-2352
78. Tsuda S., Kosaka Y., Matsusaka N., and Sasaki Y.F. Detection of pyrimethamine-induced DNA damage in mouse embryo and maternal organs by the modified alkaline single cell gel electrophoresis assay. Mutat. Res. 415 (1998) 69-77
79. Yeh Y.C., Lai H.C., Ting C.T., Lee W.L., Wang L.C., Wang K.Y., Lai H.C., and Liu T.J. Protection by doxycycline against doxorubicin-induced oxidative stress and apoptosis in mouse testes. Biochem. Pharmacol. 74 (2007) 969-980