Induction and transmission of chemically induced chromosome aberrations in female germ cells

Abstract

Female mice were dosed with a number of chemical clastogens. The dosed females were then mated 28.5, 6.5, and 0.5 days after dosing, corresponding to various developmental stages of oogenesis (ie, early pre-antral to late antral stages). One-cell embryos derived from these mating were then isolated and analysed for structural and/or numerical chromosome aberrations. Chromosome damage, either structural or numerical, was induced only in oocytes at the late antral stages of oogenesis (i.e. when females were dosed 0.5 days prior to mating). There were few chromosome aberrations in embryos obtained from females dosed 6.5 or 28.5 days prior to mating. The results show that the analysis of one-cell embryos derived from the germ cells of dosed females is a potentially useful test system for the identification of chemically induced structural and numerical chromosome aberrations. However, the technically demanding methods involved in the preparation of these one-cell embryos prevent their use for routine screening purposes.

Nicotine-induced Disturbances of Meiotic Maturation in Cultured Mouse Oocytes: Alterations of Spindle Integrity and Chromosome Alignment

“…Studies on the effects of other alkaloids on oocyte meiosis using chromosome analysis found comparable results. Vinblastine sulfate administered in vivo into female mice induced dose-related increases in the proportion of oocytes arrested in M-I; this was caused by inhibition of spindle microtubules, resulting in blockage in M-I [ 45 - 47 ]. In these studies diploid oocytes which have not yet formed a polar body were found; our study confirms a dose-response for oocyte diploidy from nicotine.…”

Effects of Chemotherapy on Fertility Preservation in Patients with Tumors of the Hematopoietic and Lymphoid Tissues

“…Although not yet definitive in human studies, data from animal studies indicate that chemotherapy/radiotherapy may be mutagenic to germ cells at various maturation stages [11][12][13][14][15][16]. Therefore, it may not be advisable to collect oocytes immediately after exposure to chemotherapy.…”

Preclinical Approaches to the Protection of Ovarian Function

“…22 9.2.1 Imatinib c-Abl protein tyrosine kinase has been shown to act as a "switch" for TAp63 transcriptional activity and the apoptotic pathway following exposure to the chemotherapy agents cisplatin 19 and DXR. One important concern with developing any agent that interferes with the apoptotic pathway as a potential protectant is that, since induction of apoptosis is a key anticancer action of many of the chemotherapy drug classes, interference with the apoptotic pathway may inhibit the anticancer effects of these drugs.…”