Abstract:
:Primary mixed cultures of Sertoli and germ cells were prepared from testes of immature rats and their response to the known testicular toxicants ethylene glycol monomethyl ether (EGM) and ethylene glycol monoethyl ether (EGE) was studied. Neither EGM nor EGE produced any morphological evidence of toxicity when added to the culture medium at up to 50 mM for 72 hr. In contrast, their metabolites methoxyacetic acid (MAA) and ethoxyacetic acid (EAA) at 2 to 10 mM for 24 to 72 hr caused degeneration of the pachytene and dividing spermatocytes, the target cells of the parent ethers in vivo. As in vivo, earlier spermatocytes, spermatogonia, and Sertoli cells appeared unaffected. EAA was less potent than MAA whereas n-propoxy- and n-butoxyacetic acid, and methoxyacetylglycine, a further metabolite of MAA, produced no morphological changes under these conditions. The same order of toxicity was observed in concurrent studies with the four acids in rats. In culture, the severity of the morphological changes was paralleled by decreases in the activity of carnitine acetyltransferase and lactate dehydrogenase-X in the attached germ cell fraction. Analysis of culture medium provided no evidence for the conversion of EGM to MAA or other metabolites or for the further metabolism of MAA. The close correspondence between the testicular toxicity of alkoxyacetic acids in culture and in vivo suggests a similar mode of action in both cases and points to the potential value of these cultures for mechanistic studies and for screening purposes. The results also emphasize the role of metabolism in the testicular toxicity of glycol ethers and indicate that MAA is an active metabolite of EGM.
journal_name
Toxicol Appl Pharmacoljournal_title
Toxicology and applied pharmacologyauthors
Gray TJ,Moss EJ,Creasy DM,Gangolli SDdoi
10.1016/0041-008x(85)90146-2subject
Has Abstractpub_date
1985-07-01 00:00:00pages
490-501issue
3eissn
0041-008Xissn
1096-0333journal_volume
79pub_type
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