Abstract
Following fusion with hamster eggs, human sperm chromosomes from six Hodgkin's disease patients were analyzed to determine the genotoxic effects of therapy. Each patient had received two to six cycles of MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone), with or without radiotherapy, from 3 to 20 years before the study. A total of 571 cells from the six patients were analyzed; 9.8% of the cells had structural aberrations, and 1.6% were hyperhaploid. Analysis of 5998 metaphases from a control group of 24 male donors revealed only 6.9% of cells with structural aberrations and 0.8% aneuploidy. The increase in hyperhaploidy in the patients was statistically significant. Thus, results of this study suggest that the MOPP regimen, with or without radiotherapy, is capable of causing chromosome abnormalities in the sperm of Hodgkin's disease patients.
Similar content being viewed by others
References
Aubier FF, Flamant F, Brauner R, Caillaud JM, Chaussain JM, Lemerle J (1989) Male gonadal function after chemotherapy for solid tumors in childhood. J Clin Oncol 7:304–309
Braekeleer M de, Dao TN (1991) Cytogenetic studies in male infertility: a review. Hum Reprod 6:245–250
Brandriff BF, Gordon LA (1990) Human sperm cytogenetics and the one-cell zygote. In: Allen JW, Bridges BA, Lyon MS, Moses MJ, Russell LB (eds) Banbury report 34: biology of mammalian germ cell mutagenesis. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pp 183–194
Brandriff B, Gordon L, Watchmaker G (1985) Human sperm chromosomes obtained from hamster eggs after sperm capacitation in TEST-yolk buffer. Gamete Res 11:253–259
Brandriff BF, Gordon LA, Sharlip I, Carrano AV (1987) Sperm chromosome analysis in a survivor of seminoma and associated radiotherapy. Environ Mol Mutagen 9 (Suppl 8): 19
Brandriff BF, Gordon LA, Moore D II, Carrano AV (1988) An analysis of structural aberrations in human sperm chromosomes. Cytogenet Cell Genet 47:29–36
Cundiff JH, Cunningham JR, Golden R, Lanzl LH, Meurk ML, Ovadia J, Page Last V, Pope RA, Sampiere VA, Saylor WL, Shalek RJ, Suntharalingham N (1973) A method for the calculation of dose in the radiation treatment of Hodgkin's disease. Am J Roentgenol Radiat Ther Nucl Med 117:30–44
Cunha MF da, Meistrich ML, Fuller LM, Cundiff JH, Hagemeister FB, Velasquez WS, McLaughlin P, Riggs SA, Cabanillas FF, Salvador PG (1984) Recovery of spermatogenesis after treatment for Hodgkin's disease: limiting dose of MOPP chemotherapy. J Clin Oncol 2:571–577
Cunha M da, Meistrich ML, Samaan NA (1988) Gonadal toxicity from chemotherapy and radiotherapy for lymphomatous disease. In: Fuller LM, Hagemeister FB, Sullivan MP, Velasquez WS (eds) Hodgkin's disease and non-Hodgkin's lymphomas in adults and children. Raven Press, New York, pp 186–200
De Vita VJ Jr, Simon RM, Hubbard SM, Young RC, Berard CW, Moxley JH, Frei E, Carbone PP, Canellos GP (1980) Curability of advanced Hodgkin's disease with chemotherapy: longterm follow-up of MOPP-treated patients at the National Cancer Institute. Ann Intern Med 92:587–595
Genesca A, Caballin MR, Miro R, Benet J, Bonfill X, Egozcure J (1990) Human sperm chromosomes: long-term effect of cancer treatment. Cancer Genet Cytogenet 46:251–260
Genesca A, Caballin MR, Miro R, Benet J, Germa JR, Egozcure J (1992) Repair of human sperm chromosome aberrations in the hamster egg. Hum Genet 89:181–186
Gradishar WJ, Schilsky RL (1988) Effects of cancer treatment on the reproductive system. Crit Rev Oncol Hematol 8:153–171
Hagemeister FB, Fuller LM, Velasquez WS, Sullivan JA, North L, Butler JJ, Johnston DA, Shullenberger CC (1982) Stage I and II Hodgkin's disease: involved-field radiotherapy versus extended-field radiotherapy versus involved-field radiotherapy followed by six cycles of MOPP. Cancer Treat Rep 66:789–798
Hagemeister FB, Fuller LM, Velasquez WS, McLaughlin P, Redman JR, Swan F, Rodriguez MA, North L, Dixon D, Silvermintz K, Cabanillas F (1991) Two cycles of MOPP and radiotherapy: effective treatment for stage IIIA and IIIB Hodgkin's disease. Ann Oncol 2:25–31
Holmes GE, Holmes FF (1978) Pregnancy outcome of patients treated for Hodgkin's disease: a controlled study. Cancer 41: 1317–1322
Jenderny J, Rohrborn G (1987) Chromosome analysis of human sperm. I. First results with a modified method. Hum Genet 76:385–388
Jenderny J, Jacobi ML, Rüger A, Röhrborn G (1992) Chromosome aberrations in 450 sperm complements from eight controls and lack of increase after chemotherapy in two patients. Hum Genet 90:151–154
Longo DL, Young RC, Wesley M, Hubbard SM, Duffey PL, Jaffe ES, DeVita VT Jr (1986) Twenty years of MOPP therapy for Hodgkin's disease. J Clin Oncol 4:1295–1306
Martin RH (1989) Segregation analysis of translocations by the study of human sperm chromosome complements (invited editorial). Am J Hum Genet 44:461–463
Martin RH, Hildebrand K, Yamamoto J, Rademaker A, Barnes M, Douglas G, Arthur K, Ringrose T, Brown IS (1986) An increased frequency of human sperm chromosomal abnormalities after radiotherapy. Mutat Res 174:219–225
Martin RH, Rademaker A, Hildebrand K, Barnes M, Arthur K, Ringrose T, Brown IS, Douglas G (1989) A comparison of chromosome aberrations induced by in vivo radiotherapy in human sperm and lymphocytes. Mutat Res 226:21–30
Martin RH, Barclay L, Hildebrand K, Ko E, Fowlow SB (1990) Cytogenetic analysis of 400 sperm from three translocation heterozygotes. Hum Genet 86:33–39
Matsuda Y, Tobari I (1989) Repair capacity of fertilized mouse eggs for X-ray damage induced in sperm and mature oocytes. Mutat Res 210:35–47
Meistrich ML (1986) Relationship between spermatogonial stem cell survival and testis function after cytotoxic therapy. Br J Cancer 53 [Suppl 7]: 89–101
Mulvihill JJ, McKeen EA, Rosner F, Zarrabi MH (1987) Pregnancy outcome in cancer patients. Cancer 60:1143–1150
Ortin TTS, Shostak CA, Donaldson S (1990) Gonadal status and reproductive function following treatment for Hodgkin's disease in childhood: the Stanford experience. Int J Radiat Oncol Biol Phys 19:873–880
Rodgers RW, Fuller LM, Hagemeister FB, Johnston DA, Sullivan JA, North LB, Butler JJ, Velasquez WS, Conrad FG, Shullenberger CC (1981) Reassessment of prognostic factors in stage IIIA and IIIB Hodgkin's disease treated with MOP and radiotherapy. Cancer 47:2196–2203
Sonta S, Yamada M, Tsukasaki M (1991) Failure of chromosomally abnormal sperm to participate in fertilization in the Chinese hamster. Cytogenet Cell Genet 57:200–203
Viviani S, Santoro A, Ragni G, Bonfante V, Bestetti O, Gonadonna G (1985) Gonadal toxicity after combination chemotherapy for Hodgkin's disease: comparative results of MOPP-ABVD. Eur J Cancer Clin Oncol 21:601–605
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Brandriff, B.F., Meistrich, M.L., Gordon, L.A. et al. Chromosomal damage in sperm of patients surviving Hodgkin's disease following MOPP (nitrogen mustard, vincristine, procarbazine, and prednisone) therapy with and without radiotherapy. Hum Genet 93, 295–299 (1994). https://doi.org/10.1007/BF00212026
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00212026