DI-(2-ethylhexyl) phthalate-induced cell proliferation is involved in the inhibition of gap junctional intercellular communication and blockage of apoptosis in mouse Sertoli cells.
Di-(2-ethylhexyl) phthalate (DEHP) has been studied on gap junctional intercellular communication (GJIC) and apoptosis in cultured normal mouse Sertoli cells. Since the inhibition of GJIC and programmed cell death or apoptosis play important roles in tumor promotion and developmental toxicity, it has been hypothesized that tumor promoters may inhibit apoptosis by blocking GJIC. The results showed that the most significant downregulation of GJIC was detected at 9 h after DEHP treatment. However, a significant concentration-dependent pattern was not observed at concentrations of 100 and 500 microM, but there was a time-dependent recovery of GJIC. DEHP inhibited the apoptotic changes in the cells such as chromatin condensation, nuclear fragmentation, and the cleavage of poly(ADP-ribose) polymerase. Morphological changes related to apoptosis appeared in the nontreated cells after 12 h of serum deprivation. These morphological changes were significantly reduced in the TM5 Sertoli cells treated with 500 microM DEHP for 24 h. These results suggest that DEHP inhibited apoptosis in this cell line, preceded by the downregulation of GJIC. It was also found that DEHP reduced the phosphorylation of Cx43, which might partly explain the mechanism of inhibition of GJIC.
Kang
Kyung-Sun
KS
Department of Veterinary Public Health, College of Veterinary Medicine, School of Agricultural Biotechnology, Seoul National University, Suwon, Korea.
Lee
Yong-Soon
YS
Kim
Hyung-Sub
HS
Kim
Sung Hoon
SH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002450:Cell Communication / Q000187:drug effects*; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects*; D004051:Diethylhexyl Phthalate / Q000494:pharmacology*; D015536:Down-Regulation; D017629:Gap Junctions / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D010766:Phosphorylation; D012708:Sertoli Cells / Q000187:drug effects / Q000502:physiology
D004051:Diethylhexyl Phthalate