[Study on the endocrine disrupting effect of dimethachlon].
OBJECTIVE
In order to study the endocrine disrupting effect of dimethachlon (NDPS) (estrogenic and antiandrogenic activity).


METHODS
To investigate the estrogenic activity of NDPS by different experiments: (1) Carassius auratus received intraperitoneal injections with NDPS (0, 50, 100 and 200 mg/kg) at regular intervals (5 days) for the synthesis of VTG. The estrogenic effects of the treatment were investigated on VTG in plasma and liver measured by ELISA at 14th. (2) Added the positive control E2 (10(-7) mol/L), and NDPS (10(-10) mol/L, 10(-9) mol/L, 10(-8) mol/L, 10(-7) mol/L, 10(-6) mol/L, 10(-5) mol/L and 10(-4) mol/L) to MCF-7 cells and determinated the proliferation of MCF-7 cells with MTT assay. (3) female mices 18-22 g in weight were castrated, then they were gavaged daily for 5 days with E2 (500 microg/kg) or NDPS (0, 125, 250 and 500 mg/kg) or peanut oil, then uterus was removed and weighed at 6th. Hershberger assay: male SD rats of 4 weeks age were castrated, after 2 weeks, the other groups were dosed daily for 7 days with testosterone propionate (1 mg/kg, sc) plus peanut oil (p.o) or plus NDPS (30 mg/kg, 60 mg/kg and 120 mg/kg, p.o) but one group of castrated rats were subcutaneously injected with peanut oil plus (sc) peanut oil (p.o) as control. Then, the adrenals, prostate, glans penis, seminal vesicle, levator ani and bulbocavernosus muscles were removed and weighed.


RESULTS
Compared with control group. There have significantly increase in the plasma VTG concentration in 10 mg/kg of E2 treatment group as well as in 100 mg/kg and 200 mg/kg of NDPS 14 d after injection. In addition, a significantly increase in the liver VTG concentration was observed in the 200 mg/kg of NDPS treatment group. There was no significant alteration of Ca2+, total protein and liver protein content in plasma in all NDPS treatment groups, but E2 increased the plasma Ca2 level, that is higher than the control group. 10(-8) mol/L,10(-7) mol/L and 10(-6) mol/L NDPS could stimulate the proliferation of MCF-7 cell, and there were significant differences compared with control group. All NDPS treatment groups could increase the weight of uterus, but only 250 mg/kg group has signifgicant differences, compared with the control group. In Hershberger assay, relative weight of prostate, seminal vesicle, levator ani and bulbocavernous muscle in 60 mg/kg group and 120 mg/kg group were significantly decreased when compared with those in the control group.


CONCLUSIONS
NDPS exerts endocrine disrupting effect including estrogenic activity and antiandrogenic activity.
Chen
Jiang
J
Zhejiang Provincial Center for Disease Prevention and Control, Hangzhou 310051, China. chenjiang1977@yahoo.com.cn
Zhang
Ronghua
R
Mao
Guangming
G
Chen
Yuman
Y
D000726:Androgen Antagonists / Q000633:toxicity*; D000818:Animals; D001943:Breast Neoplasms / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002722:Chlorobenzenes / Q000633:toxicity*; D052244:Endocrine Disruptors / Q000633:toxicity*; D004968:Estrogens, Non-Steroidal / Q000633:toxicity*; D005260:Female; D006054:Goldfish; D006801:Humans; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D051381:Rats; D017207:Rats, Sprague-Dawley; D013388:Succinimides / Q000633:toxicity*; D014819:Vitellogenins / Q000032:analysis
D000726:Androgen Antagonists; D002722:Chlorobenzenes; D052244:Endocrine Disruptors; D004968:Estrogens, Non-Steroidal; D013388:Succinimides; D014819:Vitellogenins; C488805:dimethachlon