Estrogenic xenobiotics affect the intracellular activation signal in mitogen-induced human peripheral blood lymphocytes: immunotoxicological impact.
The present study was an attempt to elucidate the effect of estrogenic xenobiotics on the proliferation of mitogen-stimulated human peripheral blood lymphocyte (PBL). Our findings follow: (a) the proliferation of PBL in response to phytohemagglutinin (PHA) was mediated by protein kinase C activity, but estrogenic xenobiotics had a strong inhibitory effect on protein kinase C activity of PHA-stimulated PBL; (b) cytoplasmic extracts from PHA-stimulated PBL greatly activated DNA replication, but estrogenic xenobiotics had a strong inhibitory effect on these activities. The results suggest that the cytoplasmic signal-generating system in mitogen-treated PBL is inhibited by estrogenic xenobiotics, and that the defect occurs at all stages in the sequence of events leading to DNA synthesis and cell proliferation.
Sakabe
K
K
Department of Anatomy, Tokai University School of Medicine, Isehara, Kanagawa, Japan. sakbel@ibm.net
Okuma
M
M
Kazuno
M
M
Yamaguchi
T
T
Yoshida
T
T
Furuya
H
H
Kayama
F
F
Suwa
Y
Y
Fujii
W
W
Fresa
K L
KL
D000328:Adult; D002478:Cells, Cultured; D004261:DNA Replication / Q000187:drug effects; D004958:Estradiol / Q000494:pharmacology; D045166:Estradiol Congeners / Q000494:pharmacology*; D005260:Female; D006801:Humans; D008213:Lymphocyte Activation / Q000187:drug effects*; D008214:Lymphocytes / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects*; D015262:Xenobiotics / Q000494:pharmacology*
D045166:Estradiol Congeners; D015262:Xenobiotics; D004958:Estradiol; D011493:Protein Kinase C