Radiation- and chemical-induced structural chromosome aberrations in human spermatozoa

Abstract

Previous studies on the clastogenic effects of mutagens on human sperm chromosomes were reviewed.A marked increase of structural chromosome aberrations has been reported in the spermatozoa irradiated in vitro with five kinds of ionizing radiation ( 137 Cs gamma-, 60 Co gamma-, X-, and 3 H beta-rays and 252 Cf neutrons). The micronucleus test with hybrid 2-cell embryos generated from human sperm and hamster oocytes was shown to be useful as a simple and rapid method for assessing the effects of radiation. Radiosensitivity of human spermatozoa was highest, being followed by golden hamster, Chinese hamster and mouse spermatozoa.Chromosome-damaging effects were also found with some chemicals (bleomycin, daunomycin, methyl methanesulfonate, triethylenemelamine, neocarzinostatin, N-methyl-N'-nitro-N-nitorosoguanidine, and mitomycin C), but not with other chemicals (urethane, nitrobenzene, dioxin, cyclophosphamide, benzo(a)pyrene, and N-nitrosodimethylamine). The clastogenicity of chemical metabolites was confirmed for cyclophosphamide and benzo(a)pyrene, by using the S9-based metabolic activation system. The results of sperm chromosome analysis from cancer patients who had undergone radio-and/or chemotherapy were contradictory among investigators and further studies are necessary. The importance of mutagenicity testing with human spermatozoa is discussed.

Fluorescence in situ hybridisation analysis of chromosomal aberrations in gastric tissue: the potential involvement of Helicobacter pylori

“…Also, the gastric normal tissue in this patient was analysed separately and when compared to the gastric normal tissue from the other patients in this study, chromosomal abnormalities were higher. This may possibly suggest induced aneuploidy by the chemotherapy treatment, as has been shown in other studies (Acar et al, 2001;Kamiguchi and Tateno, 2002;Silva et al, 2002;Frias et al, 2003), but numbers are obviously too small to confirm this. Furthermore, in several cases, multiple brushes were taken from the same tumour to study intratumoural heterogeneity.…”

Declaring the existence of human germ‐cell mutagens

“…b There are two studies, both in mice [Yauk et al, 2007;Marchetti et al, 2011]. These agents induce similar biomarker effects in humans as they do in animals, such as DNA damage in sperm, as reviewed for ionizing radiation and chemotherapy [Kamiguchi and Tateno, 2002], smoking [DeMarini, 2004], and air pollution [Somers, 2011]. Thus, there is sufficiently strong mechanistic evidence for how these agents affect animals and humans.…”

Critical Aspects of Detection of Sperm DNA Fragmentation by Tunel/Flow Cytometry

“…The type of breakage detected by TUNEL is relevant, as the oocyte repair systems [Genesc a et al, 1992] may not have the same efficacy to repair the two types of DNA breaks. Double-strand DNA nicks are likely less prone to be repaired [Alvarez 2005] leading to chromosome aberrations [Richardson and Jasin 2000] in the early zygote [Kamiguchi and Tateno 2002;Derijck et al 2007].…”

“…However, the idea that the intensity of damage per cell and the quality (i.e., the type) of damage are also important is emerging [Alvarez 2005;Lewis et al 2008]. In particular, it is believed that these factors may influence the ability of the oocyte to remove the damage and hence the outcome of the repair process [Kamiguchi and Tateno 2002;Derijck et al 2007]. Another poorly considered point is the ability of a test to gain full access to the sperm chromatin.…”