Abstract
Several recent studies indicate declines in sperm production, as well as increases in the incidence of genitourinary abnormalities such as testicular cancer, cryptorchidism and hypospadias (Toppari et al., 1996). It is not known if these effects are due to exposure to chemical pollutants or if other ethiological factors are involved. Animal studies indicate that chemicals will induce such effects by various genetic, epigenetic or non-genetic mechanisms. Recently, much attention has been focused on embryonic/fetal exposure to oestrogen-mimicking chemicals (Toppari et al., 1996). However, the possibility that chemicals may cause reproductive toxicity by other mechanisms such as interactions with DNA, should not be ignored. DNA damage in germ cells may lead to the production of mutated spermatozoa, which in turn may result in spontaneous abortions, malformations and/or genetic defects in the offspring. Regarding the consequences of DNA alterations for carcinogenesis it is possible that genetic damage may occur germ cells, but the consequences are not expressed until certain genetic events occur in postnatal life. Transmission of genetic risk is best demonstrated by cancer-prone disorders such as hereditary retinoblastoma and the Li-Fraumeni syndrome. A number of experiments indicate that germ cells and proliferating cells may be particularly sensitive to DNA damaging agents compared to other cells (Masters et al., 1993; Holme et al., 1997).
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References
Barnes DE, Lindahl T, Sedgwick B (1993) DNA Repair. Curr Opinion Cell Biol 5: 424–433
Bjelland S, Eide L, Time RW, Stote R, Eftedal I, Volden GM, Seeberg E (1995) Oxidation of thymine to 5-formyluracil in DNA: mechanisms of formation, structural implications, and base excision by human cell free extracts. Biochemistry 34: 147598–147646
Bjorge C, Brunborg G, Wiger R, Holme HA, Scholz T, Dybing E, Soderlund EJ (1996b) A comparative study of chemically induced DNA damage in isolated human and rat testicular cells. Reprod Toxicol 10: 509–519
Bj0rge C, Wiger R, Holme JA, Brunborg G, Andersen R, Dybing E, Soderlund EJ (1995) In vitro toxicity of 1,2-dibromo-3-chloropropane ( DBCP) in different testicular cell types from rats. Reprod Toxicol 9: 461–473
Bjerge C, Wiger R, Holme JA, Brunborg G, Scholz T, Dybing E, Soderlund EJ (1996a) DNA strand breaks in testicular cells from humans and rats following in vitro exposure to 1,2-dibromo-3-chloropropane ( DBCP ). Reprod Toxicol 10: 51–59
Boiteux S, Belleney J, Roques BP, Laval J (1984) Two rotameric forms of open ring 7- methylguanine are present in alkylated polynucleotides. Nucl Acid Res 12: 5429–5439
Bradley MD, Dysart G (1985) DNA single-strand breaks, double-strand breaks and crosslinks in rat testicular germ cells: measurement of their formation and repair by alkaline and neutral filter elution. Cell Biol Toxicol 1: 181–512
Brunborg G, Holme JA, Hongslo JK (1995) Inhibitory effects of paracetamol on DNA repair in mammalian cells. Mutat Res 342: 157–170
Brunborg G, Holme JA, Soderlund EJ, Omichinski JG, Dybing E (1988) An automated alkaline elution system. DNA damage induced by 1,2-dibromo-3-chloropropane in vivo and in vitro. Anal Biochem 174: 522–36
Chresta CM, Masters JRW, Hickman JA (1996) Hypersensitivity of human testicular tumors to etoposide-induced apoptosis is associated with functional p53 and a high Bax:Bcl-2 ratio. Cancer Res 56: 1834–1841
Dolganov GM, Maser RS, Novikov A, Tosto L, Chong S, Bressan DA, Petrini JHJ (1996) Human Rad5o is physically associated with human Mre11: identification of a conserved multiprotein complex implicated in recombination DNA repair. Mol Cell Biol 16: 4832–4841
Dybing E, Omichincki JG, Soderlund EJ, Brunborg G, Lag M, Holme JA, Nelson SD (1989) Mutagenicity and organ damage of 1,2-dibromo-3-chloropropane (DB(7,P) and tris(2,3-dibromopropyl)phosphate (Tris-BP): role of metabolic activation. In Hodgson E, Bend JR, Philpot RM, (eds.) Reviews in biochemical toxicology. Vol. 10, Elsevier Science Publishing Co., New York; pp 139–187
Eide L, Bjeras M, Pirovano M, Alseth I, Berdal KG, Seeberg E (1996) Base excision of oxidative purine and pyrimidine DNA damage in Saccharomyces cerevisiae by a DNA glycosylase with sequence similarity to endonuclease III from Escherichia coli. Proc Natl Acad Sci 93x0735–10740
Henriks(n K, Kulmala J, Toppari J, Mehrotra K, Parvinen M (1996) Stage-specific apoptosis in the rat seminiferous epithelium: quantitation of irradiation effects. J Androl 17: 394–402
Hittmair A, Rogatsch H, Mikuz G, Feichtinger H (1994) Quantification of spermatogenesis by dual-parameter flow cytometry. Fertil Steril 61: 746–750
Holme JA, Soderlund EJ, Brunborg G, Omichinski JG, Bekkedal K, Trygg B, Nelson SD, Dybing E (1989) Different mechanisms are involved in DNA damage, bacterial mutagenicity and cytotoxicity induced by 1,2-dibromo-3-chloropropane in suspensions of rat liver cells. Carcinogenesis 10: 49–54
Holme JA, Wiger R, Hongslo JK, Soderlund EJ, Brunborg G, Dybing E (1997) Cell death via interactions of agents with DNA. Adv Mol Cell Biol 20: 145–182
Hsueh AJW, Eisenhauer K, Chun S-Y, Hsu S-Y, Billig H (1996) Gonadal cell apoptosis. Rec Prog Horm Res 51: 433–456
Humphreys WG, Kim DH, Guengerich FP (1991) Isolation and characterization of N7guanyl adducts derived from 1,2-dibromo-3-chloropropane. Chem Res Toxicol 4: 445453
Joshi DS, Yick J, Murray D, Meistrich ML (1990) Stage dependent variation in the radiosensitivity of DNA in developing germ cells. Radiat Res 121: 274–281
Kangasniemi M, Kaipia A, Mali P, Toppari J, Huhtaniemi I, Parvinen M (1990) Modulation of basal and FSH-dependent cyclic AMP production in the rat seminiferous tubules staged by an improved transillumination technique. Anat Rec 227: 62–76
Lithdetie J, Kaukopuro S, Parvinen M (1983) Genetoxic effects of ethyl methanesulfonate and X-rays at different stages of rat spermatogenesis, studied by inhibition of DNA synthesis and induction of DNA repair in vitro. Hereditas 99: 269278
Masters JRW, Osborne EJ, Walker MC, Parris CN (1993) Hypersensitivity of human testis-tumour cell lines to chemotherapeutic drugs. Int J Cancer 53340–346
Meistrich ML, Longtin J, Brock WA, Grimes SR JR, Mace ML (1981) Purification of rat spermatogenic cells and preliminary biochemical analysis of these cells. Biol Reprod 25: 1065–1077
Muris DFR, Bezzubova O, Buerstedde J-M. Vreeken K, Balajee AS, Osgood CJ, Troelstra C, Hoeijmakers JHJ, Ostermann K, Schmidt H, Natarajan AT, Eeken JCJ, Lohman PHM, Pastink A (1994) Cloning of human and mouse genes homologous to RAD52, a yeast gene involved in DNA repair and recombination. Mutat Res 315: 295–305
Oko RJ, Jando V, Wagner CL, Kistler WS, Hermo LS (1996) Chromatin reorganization in rat spermatids during the disappearance of testis-specific histone, Hit, and the appearance of transition proteins TP1 and TP2. Biol Reprod 54: 1141–1157
Omichinski JG, Soderlund EJ, Bausano JA, Dybing E, Nelson SD (1987) Synthesis and mutagenicity of selectively methylated analogs of 1,2-dibromo-3-chloropropane and tris(2,3-dibromopropyl)phosphate. Mutagenesis 2: 287–292
Omichinski JG, Brunborg G, Holme JA, Soderlund EJ, Nelson SD, Dybing E (1988) The role of oxidative and conjugative pathways in the activation of 1,2 dibromo-3chloropropane to DNA damaging products in testicular cells. Mol Pharmacol 34: 7479
Riazuddin S, Lindahl T (1978) Properties of 3-methyl-adenine-DNA-glycosylase from Escherichia coli. Biochemistry 17: 2110–2118
Roest HP, Van Klaveren J, De Wit J, Van Gurp CG, Koken MHM, Vermey M, Van Roijen JH, Hoogerbrugge JW, Vreeburg JTM, Baarends WM, Bootsma D, Grootegoed JA, Hoeijmakers JHJ (1996) Inactivation of the HR6B ubiquitin-conjugating DNA repair enzyme in mice causes male sterility associated with chromatin modification. Cell 86: 799–810
Suter L, Koch E, Bechter R, Bobadilla M (1997) Three-parameter flow cytometric analysis of rat spermatogenesis. Cytometry 27: 61–168
Soderlund EJ, Brunborg G, Omichinski JG, Holme JA, Dahl JE, Nelson SD, Dybing E (1988) Testicular necrosis and DNA damage caused by deuterated and methylated analogs of 1,2-dibromo-3-chloropropane in the rat. Toxicol Appl Pharmacol 94: 437447
Toppari J, Larsen JC, Christiansen P, Giwercman A, Grandjean P, Guillette Jr. LJ, Jegou B, Jensen TK, Jouannet P, Keiding N, Leffers H, McLachlan JA, Meyer O, Muller J, Rajpert De Meyts W, Scheike T, Sharpe R, Sumpter J, Skakkebæk NE (1996) Male reproduction health and environmental xenoestrogens. Environ Health Perspect 104(Suppl 4):741–803
Walter CA, Lu J, Bhakta M, Zhou Z-Q, Thompson LH, McCarrey JR (1994) Testis and somatic Xrcc-i DNA repair gene expression. Somat Cell Mol Genet, 20: 451–461
Van Der Spek PJ, Visser CE, Hanaoka F, Smit B, Hagemeuer A, Bootsma D, Hoeijmakers JHJ (1996) Cloning, comparative mapping, and RNA expression of the mouse homologues of the Saccharomyces cerevisiae nucleotide excision repair gene RAD23. Genomics 31: 20–27
Wilson RE, Hoyes KP, Morris ID, Sharma HL, Hendry JH, Margison GP (1994) In Vivo Induction of 06-alkylguanine-DNA-alkyltransferase in response to indium-114m. Rad Res 138: 26–33
Wilson TM, Rivkees SA, Deutsch WA, Kelley MR (1996) Differential expression of the apurinic/apyrimidinic endonuclease (APE/ref-1) multifunctional DNA base excision repair gene during fetal development and in adult rat brain and testis. Mutat Res 362: 237–248
Yamamoto A, Taki T, Yagi H, Habu T, Yoshida K, Yoshimura Y, Yamamoto K, Matsuhiro A, Nishimune Y, Morita T (1996) Cell cycle-dependent expression of the mouse Rad51 gene in proliferating cells. Mol Gen Genet 251: 1–12
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Holme, J.A. et al. (1998). Effects of Chemical-Induced DNA Damage on Male Germ Cells. In: Seiler, J.P., Autrup, J.L., Autrup, H. (eds) Diversification in Toxicology — Man and Environment. Archives of Toxicology, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-46856-8_14
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DOI: https://doi.org/10.1007/978-3-642-46856-8_14
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