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Willem Seinen

Publications and source records attributed to Willem Seinen.

At least 19 recordsLinked to original sources
PubMed2006

Tetracyclines and tetracycline resistance in agricultural soils: microcosm and field studies.

The influence of the use of antibiotics on the prevalence of resistance genes in the environment is still poorly understood. We studied the diversity of tetracycline and sulfonamide resistance genes as influenced by fertilization with pig manure in soil microcosms and at two field locations. Manure contained a high diversity of resistance genes, regardless of whether it stemmed from a farm operation with low or regular use of antibiotics. In the microcosm soils, the influence of fertilization with manure was clearly shown by an increase in the number of resistance genes in the soil after manuring. Spiking of the tetracycline compounds to the microcosms had only little additional impact on the diversity of resistance genes. Overall, the tetracycline resistance genes tet(T), tet(W), and tet(Z) were ubiquitous in soil and pig slurries, whereas tet(Y), tet(S), tet(C), tet(Q), and tet(H) were introduced to the microcosm soil by manuring. The diversity of tetracycline and sulfonamide [sul(1), sul(2), and sul(3)] resistance genes on a Swiss pasture was very high even before slurry amendment, although manure from intensive farming had not been applied in the previous years. The additional effect of manuring was small, with the tetracycline and sulfonamide resistance diversity staying at high levels for the complete growth season. At an agricultural field site in Germany, the diversity of tetracycline and sulfonamide resistance genes was considerably lower, possibly reflecting regional differences in gene diversity. This study shows that there is a considerable pool of resistance genes in soils. Although it is not possible to conclude whether this diversity is caused by the global spread of resistance genes after 50 years of tetracycline use or is due to the natural background in soil resistance genes, it highlights a role that environmental reservoirs might play in resistance gene capture.

Agrochemicals↗
PubMed2006

On the limits of toxicant-induced tolerance testing: cotolerance and response variation of antibiotic effects.

Pollution-induced community tolerance (PICT) as an ecotoxicological test system has been claimed to detect pollutant effects highly specifically and sensitively. However, the specificity might be limited by the occurrence of cotolerance. Another limitation of the application of any ecotoxicological test system lies in variation of the measured responses. We tested the variation and the occurrence of cotolerance experimentally, using antibiotics as toxicants, soil microcosms as microbial communities, and tolerance determination in Biolog plates as PICT detection test. Bacteria have been discussed as being prone to multiple tolerances due to the possible accumulation of multiple resistance genes on mobile genetic elements. However, in our experiments, cotolerance occurred only between antibiotics of the same group (oxytetracycline and tetracycline), as expected from their identical mode of action. Cotolerance between oxytetracycline and tylosin in soil microcosms exposed to oxytetracycline was low, as was cotolerance to oxytetracycline in tylosin-exposed microcosms. We conclude that tolerance development to antibiotics in soils reflects the actual selection pressure rather than a general pattern of multiple resistances. Concerning variation, the PICT effect of tetracycline was well reproducible in two consecutive years. The response variation linked to PICT experiments in controlled microcosms was comparable to that of ecotoxicological test systems of equivalent complexity. In conclusion, our results support an application of the PICT methodology as an effective means to study the soil ecotoxicology of antibiotics.

Adsorption↗
PubMed2005

The impact of the hyperacid Ijen Crater Lake: risks of excess fluoride to human health.

The Asembagus irrigation area (East Java, Indonesia) receives a high input of fluoride (F) via surface water that partially originates from the hyperacid crater lake of the Ijen volcano. Endemic dental fluorosis among local residents has been ascribed to F in water wells. In this study, the total F intake by children and adults was estimated, based on concentrations in well waters and foods throughout the area. These values were compared with the Lowest Observed Adverse Effect Level (LOAEL) for dental fluorosis among children and skeletal fluorosis among adults. Fluorosis hazard maps were prepared, identifying the most hazardous locations in the area. It was concluded that there is not only a high risk of dental fluorosis, but also of skeletal fluorosis. Based on the total daily intake, the lowest F concentration in drinking water that poses a risk of developing fluorosis is approximately 0.5 mg/l for dental fluorosis and 1.1 mg/l for skeletal fluorosis. This is below 1.5 mg/l, which is both the guideline value for drinking water from the World Health Organization (WHO) and the Indonesian drinking water standard. This is the first documented case of human health problems that may be directly associated with natural pollutants originating from a volcano-hosted crater lake.

Drinking Behavior↗
PubMed2005

Proceedings in uncovering the mechanism behind peroxisome proliferator-induced hepatocarcinogenesis.

The cancer risk assessment of peroxisome proliferators (PPs) has been a matter of debate for decades. PPs are non-genotoxic carcinogens that cause liver tumours in rodents. There is considerable evidence that humans are refractory to the carcinogenic effect of PPs. Still, some toxicologists argue that these chemicals should be considered carcinogenic until the opposite has been proven. To solve this matter, much work has been dedicated to uncovering the mode of action of PPs. The proceedings are reviewed and it is discussed whether these provide an explanation for the observed interspecies differences and shed a new light on human health risk assessment. The efforts in the past years have significantly increased our understanding of the pathways involved, but have also raised new questions. The question why humans seem to be refractory is yet to be answered. From this point of view, the safety assessment of PPs to humans therefore remains an issue of discussion.

Animals↗
PubMed2005

CP-arene oxides: the ultimate, active mutagenic forms of cyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs).

The bacterial mutagenic response (Ames-assay, Salmonella typhimurium strain TA98+/-S9-mix) of a series of monocyclopenta-fused polycyclic aromatic hydrocarbons (CP-PAHs) identified in combustion exhausts, viz. cyclopenta[cd]pyrene (1), acephenanthrylene (2), aceanthrylene (3) and cyclopenta[hi]chrysene (4), is re-evaluated. The mutagenic effects are compared with those exerted by the corresponding partially hydrogenated derivatives, 3,4-dihydrocyclopenta[cd]pyrene (5), 4,5-dihydroacephenanthrylene (6), 1,2-dihydroaceanthrylene (7) and 4,5-dihydrocyclopenta[hi]chrysene (8). It is shown that the olefinic bond of the externally fused five-membered ring of 1, 3 and 4 is of importance for a positive mutagenic response. In contrast, whilst CP-PAH 2 is found inactive, its dihydro analogue (6) shows a weak metabolism-dependent response. The importance of epoxide formation at the external olefinic bond in the five-membered ring is substantiated by the bacterial mutagenic response of independently synthesized cyclopenta[cd]pyrene-3,4-epoxide (9), acephenanthrylene-4,5-epoxide (10), aceanthrylene-1,2-epoxide (11) and cyclopenta[hi]chrysene-4,5-epoxide (12). Their role as ultimate, active mutagenic forms, when CP-PAHs 1, 3 and 4 exhibit a positive mutagenic response, is confirmed. Semi-empirical Austin Model 1 (AM1) calculations on the formation of the CP-arene oxides (9-12) and their conversion into the monohydroxy-carbocations (9a-12a and 9b-12b) via epoxide-ring opening support our results. For 2 and 4, which also possess a bay-region besides an annelated cyclopenta moiety, the calculations rationalize that epoxidation at the olefinic bond of the cyclopenta moiety is favoured.

DNA↗
PubMed2005

Examination of the in vitro (anti)estrogenic, (anti)androgenic and (anti)dioxin-like activities of tetralin, indane and isochroman derivatives using receptor-specific bioassays.

Molecules derived from tetralin, indane and isochroman are often used in the synthesis of fragrance materials. The two polycyclic musk fragrances AHTN (6-acetyl-1,1,2,4,4,7-hexamethyltetralin), HHCB (1,2,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran) and ADBI (4-acetyl-1,1-dimethyl-6-tert-butylindane) are derived from tetralin, isochroman and indane, respectively. In previous studies, AHTN and HHCB have been shown to antagonize estrogen receptors (ERs), both in vitro and in vivo. Here, we used two newly developed reporter gene assays, to examine the agonistic and antagonistic properties of several indane, tetralin and isochroman derivatives towards the human androgen receptor (AR) and aryl hydrocarbon receptor (AhR). Additionally, we also assessed (anti)estrogenicity of these compounds. A number of compounds showed weak estrogenic activity towards the human ER alpha. Several compounds showed (anti)estrogenic effects, starting at a concentration of 0.1 microM. Surprisingly, almost all compounds were found to be AR antagonists, starting at 0.1 microM. None of the compounds tested, showed either agonism or antagonism towards the AhR. Non-specific effects via crosstalk of the AhR and the ER or AR can therefore be ruled out. As far as we are aware, molecules derived from indane, tetralin and isochroman showing direct interaction with the ER and AR have not been reported previously.

Androgen Receptor Antagonists↗
PubMed2005

The impact of the hyperacid Ijen Crater Lake. Part I: Concentrations of elements in crops and soil.

In Asembagus (East Java, Indonesia) irrigation water is contaminated with effluent from the hyperacid Ijen Crater Lake resulting in a low pH and high levels of various elements. As a first step towards a risk assessment, locally produced food items (rice, maize, cassava leaf, cassava root, peanuts) were collected and concentrations of As, B, Ca, Cd, Co, Cu, Fe, Mg, Mn, Mo, Ni, Pb, V, Zn were compared to samples from a reference area and with literature values. Further, concentrations in rice were compared to total soil concentrations in paddy fields. Compared to the reference area, food items produced in the contaminated area had increased levels of Cd, Co, Ni and Mn in particular, while levels of Mo were lower. In contrast, total soil concentrations of Cd and Mn in particular have decreased whereas especially Mo was increased. In combination with the observed soil acidification, it is likely that the bioavailable concentration of most elements in the contaminated soil is higher (except for Mo) due to an increased weathering rate and/or input via the contaminated irrigation water. In terms of human health, concentrations in foods were generally within normal literature values. However, it was observed that essential elements (in particular Fe) known for their inhibitory effects on e.g. Cd and Mn toxicity did not accumulate in crops whereas Cd and Mn did.

Crops, Agricultural↗
PubMed2005

The Impact of the hyperacid Ijen Crater Lake. Part II: A total diet study.

In Asembagus (East Java, Indonesia), surface water is contaminated with effluent from the hyperacid Ijen Crater Lake. In a previous study, we reported that food crops irrigated with this water had increased concentrations of various elements. Here, we present a total diet study for adults and 6-year-old children to determine if the mean daily intake of a broad range of elements is safe and adequate. For children, the intake of B, Mg, Mn and V is high with Hazard Quotients (HQ) of 1.1 (B), 1.4 (Mn) and 1.4 (V), respectively (no TDI is available for Mg). For Mn, the daily intake is high due to the consumption of locally produced rice. Drinking water is the main source of B, Mg and V. For adults, the intake of Mg, Mn and V is also high but HQ values are < or =0.7. For both children and adults, the intake of Ca, Zn and particularly Fe is below the RNI (Fe intake is 90% below the RNI for women). It is concluded the mean intake of elements is unbalanced and Fe deficiency is probably the most serious health problem. Toxic effects cannot be fully excluded since deficiency of essential elements such as Ca, Fe and Zn can increase the absorption and retention of various elements.

Adult↗
PubMed2005

Induction of ethoxy-resorufin-O-deethylase activity by halogenated aromatic hydrocarbons and polycyclic aromatic hydrocarbons in primary hepatocytes of the green frog (Rana esculenta).

In this study, we measured the ethoxy-resorufin-O-deethylase (EROD) activity in primary hepatocytes of the common green frog Rana esculenta as a biomarker for cytochrome P4501A induction. We exposed hepatocytes derived from male and female frogs to several halogenated aromatic hydrocarbons, such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), 2,3,4,7,8-pentachlorodibenzofuran (PCDF), polychlorinated biphenyls (PCB-126, PCB-118), and polycyclic aromatic hydrocarbons such as benzo[a]pyrene (BaP), chrysene, anthracene, and pyrene. Exposure to PCB-118, anthracene, and pyrene, up to 1 microM, did not induce EROD activity, whereas TCDD and PCDF induced EROD activity maximally. In our primary frog hepatocytes, exposure to chrysene and BaP resulted in median effective concentration values (EC50) in the high nM range (82-1035 nM). Exposure to TCDD, PCDF, and PCB-126 resulted in EC50 values of 0.4 to 8, 0.07 to 0.7, and 3 to 133 nM, respectively, which is in the same range as EC50 values found in primary hepatocytes of birds. Compared to our frog hepatocytes, primary rat hepatocytes seem to be more sensitive to TCDD, chrysene, and BaP.

Animals↗
PubMed2004

Di-epoxides of the three isomeric dicyclopenta-fused pyrenes: ultimate mutagenic active agents.

To rationalize the high bacterial mutagenic response recently found for the (di-) cyclopenta-fused pyrene congeners, viz. cyclopenta[cd]-(1), dicyclopenta[cd,mn]-(2), dicyclopenta[cd,fg]-(3) and dicyclopenta[cd,jk]pyrene (4), in the presence of a metabolic activation mixture (S9-mix), their (di-)epoxides at the externally fused unsaturated five-membered rings were previously proposed as the ultimate mutagenic active forms. In this study, cyclopenta[cd]pyrene-3,4-epoxide (5) and the novel dicyclopenta[cd,mn]pyrene-1,2,4,5-di-epoxide (6), dicyclopenta[cd,fg]pyrene-5,6,7,8-di-epoxide (7) and dicyclopenta[cd,jk]pyrene-1,2,6,7-di-epoxide (8) were synthesised from 1 to 4, respectively, and subsequently assayed for bacterial mutagenicity in the standard microsomal/histidine reverse mutation assay (Ames-assay with Salmonella typhimurium strain TA98). The di-epoxides 6-8 are present as a mixture of their cis- and trans-stereo-isomers in a close to 1:1 ratio ((1)H NMR spectroscopy and ab initio IGLO/III//RHF/6-31G** calculations). The direct-acting mutagenic activity and the strong cytotoxicity exerted by 5-8 both in the absence or presence of an exogenous metabolic activation system (+/-S9-mix) demonstrate that the ultimate mutagenic active forms are the proposed (di-)epoxides of 1-4.

Animals↗
PubMed2004

Interaction of polycyclic musks and UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone receptor (PR) in reporter gene bioassays.

Two important ingredients of personal care products, namely polycyclic musk fragrances and UV filters, can be found in the environment and in humans. In previous studies, several compounds of both classes have been tested for their interaction with the estrogen receptor. Two polycyclic musk fragrances, namely AHTN and HHCB, turned out to be anti-estrogenic both in vitro and in vivo in a transgenic zebrafish assay. Several UV filters have been shown to exert estrogenic effects in vitro and in some in vivo studies. Here, we assessed the interaction of five polycyclic musk compounds and seven UV filters with the estrogen receptor (ER), androgen receptor (AR), and progesterone (PR) receptor, using sensitive and specific reporter gene cell lines. Four polycyclic musks (AHTN, HHCB, AETT, and AHMI) were found to be antagonists toward the ERbeta, AR and PR. The UV filters that showed estrogenic effects (benzophenone-3, Bp-3; 3-benzylidene camphor, 3-BC; homosalate, HMS; and 4-methylbenzylidene camphor, 4-MBC) were found to be antagonists toward the AR and PR. The ERalpha agonistic UV filter octyl-dimethyl-p-aminobenzoic acid (OD-PABA) did not show activity toward the AR and PR. Octyl methoxy cinnamate (OMC) showed weak ERalpha agonism, but potent PR antagonism. Butyl methoxydibenzoylmethane (B-MDM) only showed weak ERalpha agonism and weak AR antagonism. Most effects were observed at relatively high concentrations (above 1 muM); however, the anti-progestagenic effects of the polycyclic musks AHMI and AHTN were detected at concentrations as low as 0.01 muM. The activity of anti-progestagenic xenobiotics at low concentrations indicates the need to undertake more research to find out about the potential endocrine disrupting effects of these compounds in vivo.

Benzopyrans↗
PubMed2004

Bacterial mutagenicity of the three isomeric dicyclopenta-fused pyrenes: the effects of dicyclopenta topology.

Cyclopenta[cd]pyrene (1) and its congeners dicyclopenta[cd,mn]- (2), dicyclopenta[cd,fg]- (3), dicyclopenta[cd,jk]pyrene (4), which were all identified as constituents of combustion exhausts, as well as their partially hydrogenated derivatives 3,4-dihydrocyclopenta[cd]- (5), 1,2,4,5-tetrahydrodicyclopenta[cd,mn]- (6), 5,6,7,8-tetrahydrodicyclopenta[cd,fg]- (7) and 1,2,6,7-tetrahydrodicyclopenta[cd,jk]pyrene (8), were assayed for mutagenicity in the Salmonella typhimurium strain TA98 using different concentrations of microsomal protein in the metabolic activation system (S9-mix, with S9-fraction from liver of Aroclor-1254-treated rats: 2, 4 and 10% (v/v), respectively). Whereas a positive mutagenic response is found for 1-4 in the presence of S9-mix, 5-8 exert no mutagenicity either with or without S9-mix. Since for 1-4 the highest response is observed with S9-mix 2% (v/v) instead of the standard 4% (v/v), a one-step activation pathway, i.e. epoxidation of the five-membered ring olefinic bonds, appears to be operational. Surprisingly, 3 and, to a lesser extent, 2 (11.7 versus 4.2 His revertants/nmol) also give a positive response in the absence of S9-mix. Hence, 2 and 3 are expected to contribute to the direct-acting mutagenicity of the non-polar fraction of combustion exhausts. Presumably for the direct-acting mutagenicity one-electron transfer processes play a role in bioactivation. The experimental observations are supported by semi-empirical AM1 calculations on the possible ultimate metabolites, i.e. mono-epoxides (2a-4a), cis-di-epoxides (2b-4b) and trans-di-epoxides (2c-4c) and the related mono-hydroxy carbocations (2d-4d and 2e-4e), and the radical anions 1*(-)-4*(-).

Cyclopentanes↗
PubMed2004

In vitro and in vivo antiestrogenic effects of polycyclic musks in zebrafish.

The polycyclic musks 6-acetyl-1,1,2,4,4,7-hexamethyltetraline (AHTN) and 1,2,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran (HHCB) are used as fragrance ingredients in perfumes, soaps, and household cleaning products. They are known to be ubiquitously present in the aquatic environment, and because of their lipophilic nature, they tend to bioaccumulate in aquatic biota. In surface waters, concentrations between 1 ng/L and 5 microg/L have been found, depending mainly on the proportion of sewage effluents in the water. In fish, under normal environmental conditions, concentrations in the microgram per kilogram fresh weight (fw) range are found. In a previous study we showed that AHTN and HHCB exert mainly antiestrogenic effects on the human estrogen receptor alpha (ERalpha) and ERbeta in an in vitro reporter gene assay. In the current study, we assessed the in vitro antiestrogenic effects of both musks on zebrafish ERs. Antagonism was observed on zfERbeta, and more pronounced on the newly cloned zfERgamma. Using a transgenic zebrafish assay, we studied antiestrogenicity of the musks in vivo. Dose-dependent antagonistic effects were observed at concentrations of 0.1 and 1 microM AHTN and HHCB. GC-MS analysis showed that the musks bioaccumulated in the fish, with internal concentrations (15-150 mg/kg fw) which were roughly 600 times higher than the nominal test doses. To our knowledge, this is the first time that environmental contaminants are shown to be antiestrogenic in an in vivo fish assay that focuses solely on ER-mediated effects. This makes the transgenic zebrafish assay a promising tool for the rapid detection of both estrogenic and antiestrogenic effects of chemicals in fish.

Animals↗
PubMed2004

Cyclopenta[cd]fluoranthene and its precursors in combustion exhausts: a survey of their bacterial mutagenic activity.

Cyclopenta[cd]fluoranthene (1) and 3-ethynylfluoranthene (2) have both recently been identified in combustion exhausts. In this study, their mutagenic activities were compared to that of fluoranthene (3), one of the most abundant polycyclic aromatic hydrocarbons (PAHs) in combustion exhausts, in the Salmonella/microsome reversion assay (Ames assay) using S. typhimurium strain TA98. The mutagenicity of 1 was modest in comparison to other active cyclopenta PAHs. Unexpectedly, 2 was mutagenic both with and without exogenous metabolic activation (rat liver S9). Furthermore, cyclopenta[cd]fluoranthene-3,4-epoxide (6) was synthesized in order to evaluate its role as the ultimate mutagenic active form of 1. The epoxide 6 was a direct-acting mutagen. In addition, a pyrolysate containing a mixture of 1 (85%), 2 (2%), and 3 (13%) obtained by flash vacuum thermolysis of 3-(1-chloroethenyl)fluoranthene (2a) at 1,050 degrees C was also mutagenic, but a significant mutagenic response was detected only in the presence of S9 activation. The results of this study indicate that 1 and 2 can contribute to the mutagenic activity of combustion exhausts.

Animals↗
PubMed2003

Calf intestinal alkaline phosphatase, a novel therapeutic drug for lipopolysaccharide (LPS)-mediated diseases, attenuates LPS toxicity in mice and piglets.

It has been demonstrated that human placental alkaline phosphatase (HPLAP) attenuates the lipopolysaccharide (LPS)-mediated inflammatory response, likely through dephosphorylation of the lipid A moiety of LPS. In this study, it is demonstrated that also alkaline phosphatase derived from calf intestine (CIAP) is able to detoxify LPS. In mice administered CIAP, 80% of the animals survived a lethal Escherichia coli infection. In piglets, previous to LPS detoxification, the pharmacokinetic behavior of CIAP was studied. CIAP clearance was shown to be dose-independent and showed a biphasic pattern with an initial t1/2 of 3 to 5 min and a second phase t1/2 of 2 to 3 h. Although CIAP is cleared much faster than HPLAP, it attenuates LPS-mediated effects on hematology and tumor necrosis factor-alpha responses at doses up to 10 microg/kg in piglets. LPS-induced hematological changes were antagonized, and the tumor necrosis factor-alpha response was reduced up to 98%. Daily i.v. bolus administration of 4000 units CIAP, the highest dose used in the LPS intervention studies, in piglets for 28 days was tolerated without any sign of toxicity. Therefore, CIAP potentially encompasses a novel therapeutic agent in the treatment of LPS-mediated diseases. Based on the data mentioned above, human clinical trials have been initiated.

Alkaline Phosphatase↗
PubMed2003

Measured pore-water concentrations make equilibrium partitioning work--a data analysis.

There is an increasing body of evidence that the bioaccumulation of sediment-associated hydrophobic organic compounds (HOCs) is strongly influenced by sequestration. At present, it is not known how equilibrium partitioning theory (EqP), the most commonly employed approach for describing sediment bioaccumulation can be applied to sediments with sequestered contaminants. In this paper, we present freely dissolved pore-water concentrations of HOCs. These data were employed to interpret sediment bioaccumulation and sequestration data in order to arrive at a process based evaluation of EqP. The data analysis suggests that sediment bioaccumulation of compounds up to log K(ow) 7.5 in Tubificidae can be described as bioconcentration from pore-water. In addition, the pore-water concentrations of HOCs (4.5 < log K(ow) < 7.5) are established by equilibrium partitioning between the rapidly desorbing HOCs fraction in the sediment and the pore-water. Taken together, these findings indicate that EqP is a conceptually correct representation of sediment bioaccumulation, provided that sequestration is accounted for. This implies that the risk assessment of sediment-associated HOCs can be significantly simplified: With a method at hand for measuring freely dissolved pore-water concentrations of HOCs, it appears that HOCs' body residues in sediment dwelling organisms can be estimated on the basis of concentrations in pore-water and bioconcentration factors.

Animals↗
PubMed2002

Transcriptional activation of estrogen receptor ERalpha and ERbeta by polycyclic musks is cell type dependent.

In the past decade the list of chemicals in the environment that are able to mimic the natural hormone estrogen, thereby disrupting endocrine function, has grown rapidly. These chemicals are able to bind to estrogen receptors (ERs) and influence estrogen signaling pathways, although several of them have structures that differ substantially from the endogenous hormone 17beta-estradiol. Because of their polycyclic nature, the polycyclic musks AHTN (6-acetyl-1,1,2,4,4,7-hexamethyltetraline) and HHCB (1,2,4,6,7,8-hexahydro-4,6,6,7,8,8-hexamethylcyclopenta-gamma-2-benzopyran) were assessed for interaction with estrogen receptors. These compounds are ubiquitously present in surface waters and have been identified in human milk fat and blood. Using sensitive in vitro reporter gene assays, we found that AHTN and HHCB act as selective estrogen receptor modulators (SERMs), inducing both estrogenic and antiestrogenic activity dependent on the cell line and the ER subtype targeted. Weak estrogenic effects were observed only at relatively high concentrations (10 microM). Antiestrogenic effects were observed in various cell lines starting at concentrations of 0.1 microM. In comparison with the well-known SERM, 4-hydroxytamoxifen, AHTN and HHCB have a much lower potency in suppressing estradiol-induced transactivation. Results with various mutant ER receptor types suggest that binding sites of the musk compounds differ from 17beta-estradiol and 4-hydroxytamoxifen. The cell type dependency of ER transactivation shows that caution should be exerted when interpreting effects of estrogenic compounds using in vitro systems.

Benzopyrans↗