Environmental oestrogens and human reproductive cancers

Miller, William R.

doi:10.1677/erc.0.0050069

Cited by 60 publications

(33 citation statements)

References 196 publications

(164 reference statements)

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“…This study is also limited in reflecting biologically relevant exposures, if the cumulative organochlorine levels measured in the plasma do not accurately represent the biologically effective levels in the relevant time window. The half-life of PCBs and p,p'-DDE range from 5 to 25 years (Smith, 1991;Wolff et al, 2000), and 10 to 50 years for p,p'-DDT (Miller and Sharpe, 1998;Turusov et al, 2002). Although age was correlated with most organochlorines, different organochlorine compounds persist for different periods of time and not all are long-lasting (Wolff et al, 2000).…”

Section: Discussionmentioning

confidence: 99%

Plasma organochlorine levels and prostate cancer risk

Aronson

Wilson

Hamel

et al. 2009

J Expo Sci Environ Epidemiol

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A case-control study was conducted to determine the association between plasma organochlorine levels and prostate cancer risk. Male clinic patients scheduled for prostate core biopsy or seeing their urologist for other conditions from 1997 through 1999 in Kingston, Ontario were eligible, excluding those with an earlier cancer. Age frequency matched controls (n ¼ 329) were compared with 79 incident prostate cancer cases. Before knowledge of diagnosis, the patients completed a questionnaire and donated 15 ml of blood for the measurement of 14 PCBs, and 13 organochlorine pesticides by gas chromatography. At least 70% of patients had detectable levels of nine PCB congeners and seven pesticides, and these chemicals were included in the risk analysis adjusted for total lipids. Geometric means for these PCB congeners, total PCBs, and p,p'-DDE are slightly lower for cases than controls, whereas the levels of p,p'-DDT and other pesticides are virtually equal. Adjusting for age and other confounders in multivariable logistic regression, odds ratios (ORs) are consistently below 1.0 for PCB congeners and total PCBs. For pesticides, most ORs are very close to the null. This study suggests that longterm low-level exposure to organochlorine pesticides and PCBs in the general population does not contribute to increased prostate cancer risk.

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Section: Discussionmentioning

confidence: 99%

Plasma organochlorine levels and prostate cancer risk

Aronson

Wilson

Hamel

et al. 2009

J Expo Sci Environ Epidemiol

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“…This indicates that prenatally expressed oestrogen receptors are functional with respect to transducing the effects of this synthetic oestrogen. In humans, an increased risk for developing breast and prostate cancer as well as cryptorchidism and low sperm counts has been hypothesised to be linked with exposure to exogenous oestrogens during gestation (Sharpe & Skakkebaek 1993, Miller & Sharpe 1998, Toppari & Skakkebaek 1998. The possible contribution of endogenous steroid hormones to the development of such abnormalities remains unclear (Shibata & Minn 2000).…”

Section: Introductionmentioning

confidence: 99%

Detection of oestrogenic activity of steroids present during mammalian gestation using oestrogen receptor alpha- and oestrogen receptor beta-specific in vitro assays

Lemmen¹,

Brink²,

Legler³

et al. 2002

Journal of Endocrinology

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Numerous steroid hormones are present in the foetus but their potential to activate oestrogen receptor (ER) and/or is largely unknown. In this study, in vitro assays were developed to rapidly and specifically detect ER or ER activation by these steroid hormones. Our results showed that several oestrogen precursors and androgens are able to activate both ER and ER . Of special interest is that some of these precursors are able to activate ER and ER at concentrations that are present during human gestation. Moreover, some precursors (dehydroepiandrosterone (DHEA) and 17-hydroxylated pregnenolone sulphate) and androgens (5-androsten-3 ,16 ,17 -triol and testosterone) showed a more than 100-fold relative preference for ER transactivation over ER transactivation when compared with 17 -oestradiol. Due to their relatively high levels, the precursor steroids DHEA and pregnenolone may be of particular importance in the regulation of ER activity in vivo. To obtain information about the oestrogenic activity of the total pool of steroid hormones present during mammalian gestation, steroids were extracted from mouse embryos at different prenatal stages and assayed for oestrogenic activity in the established in vitro assays. Oestrogenic activity was detected in steroid extracts from all stages tested. This study has demonstrated that oestrogen receptor agonists are present in the murine embryo and that oestrogen precursors may contribute to the total pool of agonists during foetal life.

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“…Man-made xenoestrogens include the alkylphenols, nonylphenol and octylphenol, and bisphenol A; environmental exposure to these compounds has been reported to modify sexual development and reproductive function in amphibians (2,3), crustacea (4,5), and fish (6). In mammals, evidence is less clear, but there is widespread public concern that they may exert similar effects on human reproductive health and be involved in the initiation of some hormone-dependent cancers (7)(8)(9)(10)(11)(12)(13)(14).…”

mentioning

confidence: 99%

Sulfation of “Estrogenic” Alkylphenols and 17β-Estradiol by Human Platelet Phenol Sulfotransferases

Harris

Waring

Kirk

et al. 2000

Journal of Biological Chemistry

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We have investigated the ability of alkylphenols to act as substrates and/or inhibitors of phenol sulfotransferase enzymes in human platelet cytosolic fractions. Our results indicate: (i) straight chain alkylphenols do not interact with the monoamine-sulfating phenol sulfotransferase (SULT1A3); (ii) short chain 4-n-alkylphenols (C < 8) are substrates for the phenol-sulfating enzymes (SULT1A1/2), which exhibit two activity maxima against substrates with alkyl chain lengths of C1-2 and C4 -5; (iii) long chain 4-n-substituted alkylphenols (C > 8) are poor substrates and act as inhibitors of SULT1A1/2; (iv) human platelets contain two activities, of low and high affinity, capable of sulfating 17␤-estradiol, and 4-n-nonylphenol is a partial mixed inhibitor of the low affinity form of this activity. We conclude that by acting either as substrates or inhibitors of SULT1A1/2, alkylphenols may influence the sulfation, and hence the excretion, of estrogens and other phenol sulfotransferase substrates in humans.

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Environmental oestrogens and human reproductive cancers

Cited by 60 publications

References 196 publications

Plasma organochlorine levels and prostate cancer risk

Plasma organochlorine levels and prostate cancer risk

Detection of oestrogenic activity of steroids present during mammalian gestation using oestrogen receptor alpha- and oestrogen receptor beta-specific in vitro assays

Sulfation of “Estrogenic” Alkylphenols and 17β-Estradiol by Human Platelet Phenol Sulfotransferases

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