Nondisjunction induced in mouse spermatogenesis by chloral hydrate, a metabolite of trichloroethylene

Abstract

The effects of chloral hydrate (CH), an in vivo metabolite of trichloroethylene, have been evaluated by cytogenetic observations of mouse secondary spermatocytes after ip treatment with 82.7, 165.4, or 413.5 mg/kg bw. Hyper-haploid metaphases have been scored to determine whether previous observations in various nonmammalian organisms about an effect of this drug on the mitotic spindle could be confirmed in mice. At each dose, the frequencies of hyper-haploid cells have been estimated to assess the response of pachytene, preleptotene, premeiotic, and staminal gonial cells. Significant increases above the control value have been observed particularly after treatment of actively dividing gonial cells, confirming the results obtained with the same batch of the drug in a parallel collaborative investigation with Aspergillus nidulans. Thus: a) chloral hydrate has been shown to be effective in inducing nondisjunction in a mammalian system; b) a prevalent action on the mitotic spindle has been confirmed and quantified; and c) the usefulness of parallel investigations with different methods is stressed, particularly to collect information about the mechanisms of induction of nondisjunction events.

Investigation of aneuploidy induction in mouse oocytes following exposure to vinblastine‐sulfate, pyrimethamine, diethylstilbestrol diphosphate, or chloral hydrate

“…Nevertheless, higher dosages of CH (300-600 mg/kg) and DESdp (200-400), even up to toxic dosages of DESdp, failed to increase the proportions of ovulated MI oocytes, polyploid oocytes, or aneuploid MI1 oocytes (Tables IV, V). The results with CH are in contrast to the observation of increased levels of aneuploidy in spermatocytes [Russo et al, 1984;Miller and Adler, 19921. The reasons for a different response in male and female germ cells remain to be determined.…”

“…CH is commonly used as an anesthetic and has been shown to destroy spindle fibers in Pleurodeles waltlii eggs [Sentein and Ates, 19741 and to inhibit spindle formation in Aspergillus nidulans [Mercer and Morris, 19751. Such interactions with the spindles are consistent with the observation of C-mitoses ("colchicine-mitoses") and multipolar spindles following CH treatment [Sentein and Ates, 1978;Dustin, 19841. CH has been reported to induce aneuploidy in mouse spermatocytes [Russo et al, 1984;Miller and Adler, 19921, but not in mouse oocytes [Mailhes et al, 19881. The studies reported here were designed to investigate further whether a qualitative difference existed for CH between male and female germ cells as indicated by our previous studies.…”

Pulmonary toxicity and carcinogenicity of trichloroethylene: species differences and modes of action.

“…Trichloroethanol glucuronide, which is the major metabolite of TCE in mice in vivo and in mouse hepatocytes in vitro, was not formed in Clara cells due to a lack of the glucuronosyltransferase enzyme catalyzing the reaction between trichloroethanol and glucuronic acid (Figure 1). Alcohol dehydrogenase, the enyme responsible for the metabolism of chloral to trichloroethanol, is also known to have low activity in the lung compared to the liver (24 (35)(36)(37), but those for aneuploidy are more consistently positive (36). However, at the present time it is not known whether aneuploidy occurs in the mouse lung.…”

Numerical and structural chromosomal abnormalities detected in human sperm with a combination of multicolor FISH assays

“…Some environmental mutagens are able to induce aneuploidy [Russo et al, 1984;Miller and Adler, 1992;Leopardi et al, 1993;Allen et al, 1995;Adler et al, 1996] and chromosomal aberrations in reproductive cells [Pacchierotti et al, 1994], e.g., translocations, deletions, or duplications of chromosomal segments. The combination of two multicolor FISH assays described in this article opens the door to future studies on the induction and persistence of numerical and structural chromosomal abnormalities in men exposed to drugs and environmental mutagens.…”