The effects of tri-o-cresyl phosphate and metabolites on rat Sertoli cell function in primary culture.
A neurotoxic organophosphate, tri-o-cresyl phosphate (TOCP) is also a testicular toxicant. Histopathologic damage in the testis is first seen in Sertoli cells. TOCP and its activated metabolite saligenin cyclic-o-tolyl phosphate (SCOTP) were evaluated for effects on rat Sertoli cells in primary culture. SCOTP, but not TOCP, caused minor morphologic effects on the cells and increased levels of lactate in the spent medium with no change in pyruvate levels, synthesis of cellular or secreted proteins, or the cyclic AMP response to FSH stimulation. SCOTP was the metabolite of TOCP that produced the largest decrease in nonspecific esterase activity in Sertoli cells (up to 80%), when tested in the concentration range found in vivo. This decrease is consistent with previous in vivo evidence. These in vitro experiments replicate previously observed in vivo biochemical effects and suggest that SCOTP is the metabolite responsible for at least some of the biochemical effects seen in the testis after TOCP exposure.
Chapin
R E
RE
Developmental and Reproductive Toxicology Group, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Phelps
J L
JL
Burka
L T
LT
Abou-Donia
M B
MB
Heindel
J J
JJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000727:Androgen-Binding Protein / Q000378:metabolism; D000818:Animals; D043182:Carboxylesterase; D002265:Carboxylic Ester Hydrolases / Q000378:metabolism; D002478:Cells, Cultured; D005640:Follicle Stimulating Hormone / Q000494:pharmacology; D007382:Intermediate Filaments / Q000187:drug effects / Q000378:metabolism; D007773:Lactates / Q000378:metabolism; D008297:Male; D008855:Microscopy, Electron, Scanning; D008870:Microtubules / Q000187:drug effects; D009943:Organophosphorus Compounds / Q000633:toxicity; D014176:Protein Biosynthesis; D011773:Pyruvates / Q000378:metabolism; D019289:Pyruvic Acid; D051381:Rats; D012708:Sertoli Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D014317:Tritolyl Phosphates / Q000378:metabolism / Q000633:toxicity*; D014746:Vimentin / Q000378:metabolism
D000727:Androgen-Binding Protein; D007773:Lactates; D009943:Organophosphorus Compounds; D011773:Pyruvates; D014317:Tritolyl Phosphates; D014746:Vimentin; C000516:2-(2-cresyl)-4H-1-3-2-benzodioxaphosphorin-2-oxide; D019289:Pyruvic Acid; D000255:Adenosine Triphosphate; D005640:Follicle Stimulating Hormone; D002265:Carboxylic Ester Hydrolases; D043182:Carboxylesterase; C025541:tri-o-cresyl phosphate