Elsevier

Mutation Research Letters

Volume 323, Issues 1–2, January–February 1994, Pages 81-88
Mutation Research Letters

Spermatid micronucleus analyses of trichloroethylene and chloral hydrate effects in mice

https://doi.org/10.1016/0165-7992(94)90049-3Get rights and content

Abstract

Mice were exposed by inhalation to trichloroethylene (TCE) or by i.p. injection to the TCE metabolite, chloral hydrate (CH). Early spermatids were analyzed for micronucleus (MN) frequency and the presence or absence of kinetochore(s) using fluorochrome-labeled anti-kinetochore antibodies. It was determined that 5 consecutive days of exposure to 5, 50 or 500 ppm TCE during preleptotene through early pachytene stages of meiotic cell development do not result in increased frequencies of spermatid MN. CH at 41, 83 or 165 mg/kg was positive for spermatid MN induction when treatments corresponded to spermatogonial stem cell or preleptotene spermatocyte stages of development; negative results were obtained after treatments of leptotene—zygotene or diakinesis—metaphase stages. The significantly increased levels of MN observed were invariably of the kinetochore-negative type.

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      CH was also found to induce significant aneugenic effects in mice [41]. Furthermore, micronuclei were produced in germ cells of male mice treated intraperitoneally with CH [42]. CH was also reported to be able to lead to chromosomal loss in mouse spermatids [43] and in human lymphocytes [44].

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      It must be emphasized the importance that the current regulations give to toxicity, to avoid false positive data due to over stressed cell [22]. Previous published results have shown that this chlorinated HA is a direct-acting mutagen that induces point mutations, increases the frequency of MN in mouse spermatocytes and cultured human fibroblasts, increases the induction of primary DNA damage in TK6 cells, and induces MN and SCE in peripheral blood lymphocytes of treated children [34,39–43]. By the contrary, negative results were obtained in cultured CHO cells (comet assay) and in TK6 cells (MN test) [34,44].

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      In terms of cytogenetic assessment, a number of studies reporting positives and negatives are described in the literature. CH was able to increase the frequency of MN in mouse spermatocytes (Russo and Levis, 1992), as well as MN and chromosome loss in germ cells of male mice (Allen et al., 1994; Nutley et al., 1996). In addition, significant increases in the frequencies of MN and SCE in blood peripheral lymphocytes have reported in infants treated with CH (Ikbal et al., 2004).

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