title: Increased frequencies of diploid sperm detected by multicolour FISH after treatment of rats with carbendazim without micronucleus induction in peripheral blood erythrocytes.
abstract: The purpose of the present study was to determine the effect of a single oral dose of carbendazim (CARB) on the frequencies of numerical chromosome aberrations in sperm and on micronuclei in peripheral blood erythrocytes of rats. Dual colour FISH on epididymal sperm of rats treated 31 days before sacrifice (0, 50, 150, 450 and 800 mg/kg body wt CARB in corn oil), corresponding to exposure during late pachytene, revealed a clear induction of diploid sperm. Induction of aneuploid sperm was not observed. Although the absolute frequencies of diploidy were low, ranging from 0.03% in the control group to 0.22% in the highest dose group, the observed dose-response relationship was highly significant. In sperm of rats killed 50 days after treatment with CARB (corresponding to exposure of spermatogonial stem cells) the effect was no longer apparent. In a second experiment, in addition to more dose groups in the low dose range, the peripheral blood micronucleus assay was incorporated. Results of triple colour FISH on epididymal sperm of rats treated with CARB (0-800 mg/kg body wt) again showed induction of diploid, but not of aneuploid sperm. Induction was less prominent than in the first experiment, but the dose-response relationship for diploidy was again significant. In blood samples drawn from the tail vein 48 h after treatment with CARB induction of micronuclei in peripheral blood erythrocytes was not observed, whereas the micronucleus frequency was significantly increased after a single i. p. dose of mitomycin C (3 mg/kg body wt). In conclusion, the present results show that CARB induces diploidy in sperm, without an accompanying induction of micronuclei in erythrocytes. This finding suggests that in rats the peripheral blood micronucleus assay is a less sensitive indicator for the genotoxic potential of CARB than the epididymal sperm aneuploidy/diploidy assay.
authors.affiliation: Laboratory of Health Effects Research, National Institute of Public Health and the Environment, PO Box 1, 3720 BA Bilthoven, The Netherlands.
authors.forename: J M
authors.initials: JM
authors.lastname: de Stoppelaar
authors.forename: T
authors.initials: T
authors.lastname: van de Kuil
authors.forename: M
authors.initials: M
authors.lastname: Bedaf
authors.forename: H W
authors.initials: HW
authors.lastname: Verharen
authors.forename: W
authors.initials: W
authors.lastname: Slob
authors.forename: G R
authors.initials: GR
authors.lastname: Mohn
authors.forename: B
authors.initials: B
authors.lastname: Hoebee
authors.forename: J
authors.initials: J
authors.lastname: van Benthem
mesh_terms: D000284:Administration, Oral; D000782:Aneuploidy; D000818:Animals; D001562:Benzimidazoles / Q000633:toxicity*; D002219:Carbamates; D004171:Diploidy; D004305:Dose-Response Relationship, Drug; D004912:Erythrocytes / Q000187:drug effects*; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008540:Meiosis; D015162:Micronucleus Tests; D009153:Mutagens / Q000633:toxicity*; D051381:Rats; D017208:Rats, Wistar; D013093:Spermatogonia / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D001562:Benzimidazoles; D002219:Carbamates; D009153:Mutagens; C006698:carbendazim