Genotoxic And Cytotoxic Effects Of Butadiene And Its Metabolites On Mouse Spermatogenesis.
M. Spanò, B. Bassani, E. Cordelli, G. Leter, C. Tiveron, and F. Pacchierotti*, Division of Environmental Toxicology, ENEA Casaccia, 00060 Rome
Butadiene (BD), a compound widely used in the industrial manufacture of rubber and plastics, is considered of high concern in occupational health (IARC 2A). After inhalation, BD undergoes a complex biotransformation pathway involving the production of epoxydes, such as diepoxybutane (DEB), considered the active metabolites responsible of the observed genetic effects. Thus, the effects of DEB and BD on the mouse reproductive system have been investigated by: i) flow cytometric (FCM) DNA content evaluation of testicular cells; ii) FCM sperm chromatin structure assay (SCSA) through bivariate analysis of acridine orange (AO) stained sperm; and, iii) cytogenetic analysis on one-cell embryos. FCM analysis evidenced a selective cytotoxic damage on the differentiating spermatogonia compartment in animal exposed to the compounds. The damage was transient and completely recovered in the next spermatogenic cycle. In addition, DEB induced a higher frequency of sperm with altered chromatin packaging as evaluated by the SCSA. The cytogenetic analysis shows that during spermiogenesis, spermatozoa, and to a lesser extent, late spermatids are sensitive to the induction of DNA damage leading to chromosome breaks and rearrangements detectable at the first cleavage division.
Work partially supported by CEC contracts STEP-CT91-0144 and EV5V-CT94-0543.