Effects of the β-isomer of hexachlorocyclohexane on estrogen-sensitive human mammary tumor cells

Coosen, R.; Velsen, F.L. van

doi:10.1016/0041-008x(89)90279-2

Cited by 36 publications

(19 citation statements)

References 19 publications

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“…Organochlorine-type pesticides should be of the most concern among the nine groups of pesticides suggested as candidates to be endocrine disruptors, because of their global distribution by widespread use and bioaccumulation through the ecosystem by high lipophilic property (Kutz et al 1991;Simonich and Hites 1995). Several of these compounds (DDT, methoxychlor, BHC, endosulfan, and dieldrin) have been reported to possess estrogenic activity by studies with animals and cells (Bulger et al 1978;Coosen and Velsen 1989;Soto et al 1995;Welch et al 1969).…”

Section: Discussionmentioning

confidence: 99%

“…Recent reports showed that several pesticides exert estrogenic and antiandrogenic activities through interaction with estrogen and androgen receptors. To date, p,p´-dichlorodiphenyl trichloroethane (DDT) (Welch et al 1969), methoxychlor (Bulger et al 1978;Cummings 1997), β-benzene hexachloride (BHC) (Coosen and Velsen 1989), endosulfan, toxaphene, and dieldrin (Soto et al 1995), and fenvalerate (Garey and Wolff 1998) have been reported as estrogenic pesticides. Recently, Andersen et al (2002) have reported that several currently used pesticides, such as methiocarb, fenarimol, chlorpyrifos, deltamethrin, and tolclofos-methyl, possess estrogenic activity on the basis of cell proliferation assay and transactivation assay using MCF-7 human breast cancer cells.…”

mentioning

confidence: 99%

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Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells.

Kojima

Katsura

Takeuchi

et al. 2004

Environ Health Perspect

460

314

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We tested 200 pesticides, including some of their isomers and metabolites, for agonism and antagonism to two human estrogen receptor (hER) subtypes, hERalpha and hERbeta, and a human androgen receptor (hAR) by highly sensitive transactivation assays using Chinese hamster ovary cells. The test compounds were classified into nine groups: organochlorines, diphenyl ethers, organophosphorus pesticides, pyrethroids, carbamates, acid amides, triazines, ureas, and others. These pesticides were tested at concentrations < 10-5 M. Of the 200 pesticides tested, 47 and 33 showed hER- and hERbeta-mediated estrogenic activities, respectively. Among them, 29 pesticides had both hERalpha and hERbeta agonistic activities, and the effects of the organochlorine insecticides beta-benzene hexachloride (BHC) and delta-BHC and the carbamate insecticide methiocarb were predominantly hERbeta rather than hERalpha agonistic. Weak antagonistic effects toward hERalpha and hERbeta were shown in five and two pesticides, respectively. On the other hand, none of tested pesticides showed hAR-mediated androgenic activity, but 66 of 200 pesticides exhibited inhibitory activity against the transcriptional activity induced by 5alpha-dihydrotestosterone. In particular, the antiandrogenic activities of two diphenyl ether herbicides, chlornitrofen and chlomethoxyfen, were higher than those of vinclozolin and p,p -dichlorodiphenyl dichloroethylene, known AR antagonists. The results of our ER and AR assays show that 34 pesticides possessed both estrogenic and antiandrogenic activities, indicating pleiotropic effects on hER and hAR. We also discussed chemical structures related to these activities. Taken together, our findings suggest that a variety of pesticides have estrogenic and/or antiandrogenic potential via ER and/or AR, and that numerous other manmade chemicals may also possess such estrogenic and antiandrogenic activities.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells.

Kojima

Katsura

Takeuchi

et al. 2004

Environ Health Perspect

460

314

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show abstract

“…In a breast carcinoma cell line, ␤-BHC was able to increase progesterone receptor (PR) content 10 and stimulate proliferation in a dose-dependent manner in the estrogen receptor positive (ERϩ) cell line MLF-7, but not in an ERϪ cell line.…”

mentioning

confidence: 99%

?-Benzene hexachloride in breast adipose tissue and risk of breast carcinoma

Zheng

Holford

Mayne

et al. 1999

Cancer

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“…For example, p,p -dichlorodiphenyl trichloroethane (DDT), methoxychlor, β-benzene hexachloride (BHC), endosulfan, toxaphene, dieldrin, and fenvalerate have been reported to have estrogenic activity via ER. [15][16][17][18][19][20] In addition, several pesticides or their metabolites, such as vinclozolin, procymidone, linuron, fenitrothion, fenthion, and p,pdichlorodiphenyl dichloroethylene (DDE), have been reported to have antiandrogenic activity via AR. [21][22][23][24][25][26][27] Andersen et al 28) reported that several currently used pesticides, such as methiocarb, fenarimol, chloropyrifos, deltamethrin, and tolclofosmethyl, possess estrogenic activity, whereas dieldrin, endosulfan, methiocarb, and fenarimol possess antiandrogenic activity.…”

Section: Effects Of Pesticides Via Ers Ar and Trsmentioning

confidence: 99%

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

Kojima

Takeuchi

Nagai

2010

JOURNAL OF HEALTH SCIENCE

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Nuclear receptors (NRs) and the aryl hydrocarbon receptor (AhR) form a ligand-dependent transcription factor that regulates the genes involved in key physiological functions such as cell growth and differentiation, development, homeostasis, and metabolism. These receptors are potential targets of endocrine-disrupting chemicals (EDCs). To date, many studies have shown that EDCs, such as plasticizers, pesticides, and dioxins, can function as ligands of NRs and AhR. In this review, we focus on recent studies showing that a variety of pesticides, intentionally released into the environment, have agonistic and/or antagonistic activity against NRs and AhR, and present our transactivation assay-based screening results for 200 pesticides against estrogen receptors (ERs), androgen receptor (AR), thyroid hormone receptors (TRs), pregnane X receptor (PXR), peroxisome proliferator-activated receptors (PPARs), and AhR. Our studies have shown that a number of pesticides possess ERα, ERβ, and PXR agonistic activity as well as AR antagonistic activity, whereas none of the pesticides affect the TRα 1 , TRβ 1 , and PPARγ-mediated signaling pathways. In addition, several of the 200 tested pesticides were found to have PPARα and AhR agonistic, and ERα and ERβ antagonistic activity. Although the activities of each of these compounds were weak compared to those of endogenous hormone or dioxins, the endocrine-disrupting potential of pesticides, particularly those which function against ERα/β, AR, and PXR, may reflect that of numerous environmental chemicals.

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Effects of the β-isomer of hexachlorocyclohexane on estrogen-sensitive human mammary tumor cells

Cited by 36 publications

References 19 publications

Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells.

Screening for estrogen and androgen receptor activities in 200 pesticides by in vitro reporter gene assays using Chinese hamster ovary cells.

?-Benzene hexachloride in breast adipose tissue and risk of breast carcinoma

Endocrine-disrupting Potential of Pesticides via Nuclear Receptors and Aryl Hydrocarbon Receptor

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