Estrogenic action of DDT and its analogs

212

Reports of reproductive abnormalities in the American alligator from Lake Apopka, Florida, have been linked to a spill of DDT and other pesticides suspected of having hormonelike activity. To determine whether environmental chemicals had the potential to function as exogenous hormones in the American alligator, we examined the ability of chemicals to bind the estrogen receptor (aER) and progesterone receptor (aPR) in a protein extract prepared from the oviduct of the alligator. In competition binding assays with [3H]17 beta-estradiol, some DDT metabolites showed inhibition of [3H]17 beta-estradiol binding to aER. A combination of DDTs demonstrated an additive decrease in [3H]17 beta-estradiol binding to aER. Modern-use chemicals such as alachlor, trans-nonachlor, endosulfan, and atrazine also competed with [3H]17 beta-estradiol for binding to the aER. To test the effect of chemicals identified in alligator eggs from Lake Apopka on [3H]17 beta-estradiol binding, we mixed these chemicals at concentrations measured in eggs in the competition binding assay. 2,2-bis(4-chlorophenyl)-N-(methoxymethyl)acetamide (p,p'-DDD) and trans-nonachlor, both found in Lake Apopka, interacted with aER, whereas others such as chlordane and toxaphene did not. Surprisingly, combinations of these chemicals decreased [3H]17 beta-estradiol binding in a greater than additive manner. To assess the ability of chemicals to interact with aPR, we performed commpetition binding assays with the synthetic progestin [3H]R5020. Most of the chemicals tested did not reduce [3H]R5020 binding to aPR, whereas endosulfan, alachlor, and kepone inhibited binding. These results provide the first evidence that environmental chemicals bind the aER and aPR from the American alligator, supporting the hypothesis that the reported reproductive abnormalities may be related to the modulation of endocrine-related responses. The findings that combinations of chemicals demonstrated a greater than additive interaction with the aER and some chemicals bind to the aPR in the competition binding assay are novel. This suggests that interactions of these chemicals with the endocrine system are complex. Images Figure 1. A Figure 1. B Figure 2. Figure 3. Figure 3. Figure 4. A Figure 4. B

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Interaction of environmental chemicals with the estrogen and progesterone receptors from the oviduct of the American alligator.

Vonier¹,

Crain²,

McLachlan³

et al. 1996

212

“…Organochlorine compounds Chlordecone (Kepone) Pest control Gellert 1978;Hammond et al 1979;Soto et al 1994Soto et al , 1995Flouriot et al 1995Dieldrin Soto et al 1994Sonnenschein et al 1995;Arnold et al 1996Endosulfan Soto et al 1994Sonnenschein et al 1995;Arnold et al 1996α-Endosulfan Soto et al 1994β-Endosulfan Soto et al 1994, 1995 DDT (technical grades and isomers) Welch et al 1969;Bitman and Cecil 1970;Soto et al 1994, 1997Lindane Soto et al 1995Methoxychlor Tullner 1961Bitman and Cecil 1970;Bulger et al 1978;Cummings andMetcalf 1994, 1995;vom Saal et al 1995;Soto et al 1995Toxaphene Soto et al 1994Sonnenschein et al 1995;Arnold et al 1996 PCBs Dielectric fluids; contaminated soils; fish Bitman and Cecil 1970;Ecobichon and MacKenzie 1974;Gellert 1978;Jansen et al 1993 Phenolics Alkylphenol ethoxylates (APEs) Cleaning agents and surfactants White et al 1994;Sumpter and Jobling 1995;Jobling et al 1996;Routledge and Sumpter 1996 4-Alkylphenols Used in manufacture of APEs Soto et al 1991Soto et al , 1995Jobling and Sumpter 1993;White et al 1994;…”

Section: Compoundmentioning

confidence: 99%

Exposure assessment for endocrine disruptors: some considerations in the design of studies.

Rice

Birnbaum

Cogliano

et al. 2003

In studies designed to evaluate exposure-response relationships in children's development from conception through puberty, multiple factors that affect the generation of meaningful exposure metrics must be considered. These factors include multiple routes of exposure; the timing, frequency, and duration of exposure; need for qualitative and quantitative data; sample collection and storage protocols; and the selection and documentation of analytic methods. The methods for exposure data collection and analysis must be sufficiently robust to accommodate the a priori hypotheses to be tested, as well as hypotheses generated from the data. A number of issues that must be considered in study design are summarized here.

“…The hallmark of estrogen response in the rodent is increased uterine weight, an effect observed with a wide range of environmental agents (Table 4). (26,(30)(31)(32)(33)(34)(35)(36)(37)(38)(39). In wildlife, feminization of alligators (40) has been attributed to organochlorine exposures.…”

Section: Timing Of Exposuresmentioning

confidence: 99%

Breast cancer risk and environmental exposures.

Wolff

Weston

1997

Although environmental contaminants have potential to affect breast cancer risk, explicit environmental links to this disease are limited. The most well-defined environmental risk factors are radiation exposure and alcohol ingestion. Diet is clearly related to the increased incidence of breast cancer in developed countries, but its precise role is not yet established. Recent studies have implicated exposure to organochlorines including DDT as a risk factor for breast cancer in the United States, Finland, Mexico, and Canada. Other investigations have discovered associations between breast cancer risk and exposures to chemical emissions and some occupational exposures. Several points must be considered in evaluating the relationship of environmental exposure to breast cancer. Among these considerations are the mechanism of tumorigenesis, timing of environmental exposure, and genetic modulation of exposure. Epidemiologic and ecologic investigations must take into account the very complex etiology of breast cancer and the knowledge that tumorigenesis can arise from different mechanisms. Thus crucial exposures as well as reproductive events related to breast cancer may occur years before a tumor is evident. Moreover, environmental contaminants may alter reproductive development, directly or indirectly, and thereby effect the course of tumorigenesis. Such alterations include change in gender, change in onset of puberty, and inhibition or promotion of tumor formation. Timing of exposure is therefore important with respect to mechanism and susceptibility. Finally, genetic polymorphisms exist in genes that govern capacity to metabolize environmental contaminants. Higher risk may occur among persons whose enzymes either are more active in the production of procarcinogens or fail to detoxify carcinogenic intermediates formed from chemicals in the environment.