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PubMed1983

Reactions of methylnitrosourea, epichlorohydrin, styrene oxide and acetoxyacetylaminofluorene with polyamino acids.

Radioactive methylnitrosourea, epichlorohydrin, styrene oxide, and N-acetoxy-2-acetylaminofluorene were reacted with 14 different polyamino acids in vitro, to determine the relative reactivity of the functional groups in amino acids. All the carcinogens reacted preferentially with polycysteine and much less with polyhistidine. Reaction was also noted with polylysine, polymethionine and polyarginine, as well as with DNA. Epichlorohydrin and styrene oxide reacted also with polyserine. Methylnitrosourea and N-acetoxy-2-acetylamino-fluorene reacted relatively more with polyhistidine as compared with the epoxides. Polycysteine, polyhistidine and polylysine were more reactive towards styrene oxide at pH 8 than at pH 6.

2-Acetylaminofluorene↗
PubMed1983

Bovine bladder and liver cell and homogenate-mediated mutagenesis of Salmonella typhimurium with aromatic amines.

Comparisons of aromatic amine activation were made by using intact cells or cell homogenates (S-9) from bovine bladder urothelium and liver. Since both liver and bladder are thought to contribute carcinogenic metabolites for bladder cancer initiation, comparisons of these two organs' relative ability to activate aromatic amines to mutagens were made. Salmonella typhimurium mutagenesis was used as an indication of mutagen production. Activation occurred in a dose dependent manner and no mutagenic response occurred unless activating cells or S-9 were present. Bladder urothelial cells metabolically activated the carcinogens, 2-amino-fluorene (AF), 2-acetylaminofluorene (AAF), 4-aminobiphenyl (4ABP), benzidine (BZ), and 2-naphthylamine (2NA) but not 1-naphythylamine (1NA), a non-carcinogen. Liver cells were less active than bladder cells in activating AF and AAF; but there was little or no hepatocyte activation of 4ABP, BZ, 2NA and 1NA. Intact bladder cells were more effective than bladder S-9 in activating AAF, but not in activating AF, 4ABP, BZ and 2NA. The liver S-9 showed more mutagenic activity with AF than did intact liver cells; the reverse was true for AAF, and bovine liver S-9 showed little or no activation of 4ABP, BZ, and 2NA. 1NA was not activated by either S-9 preparation. As was the case for intact cells, bladder S-9 was more effective than liver S-9 in activating the aromatic amines studied. The results demonstrate the capacity of bovine bladder urothelium to metabolically activate aromatic amines and suggest a role for the target organ itself in carcinogen activation. Information on the relative usefulness of intact cells versus S-9 preparations as activation systems was also obtained from these studies.

Amines↗
PubMed1985

Chemical carcinogens induce cadmium resistance and activate metallothionein genes in cadmium sensitive S49 mouse cells.

Treatment of cadmium-sensitive (Cds) metallothionein-negative S49 mouse cells with two direct-acting chemical carcinogens (N-ethylnitrosourea or N-acetoxy-2-acetylamino-fluorene) or with u.v. radiation induced a large increase in phenotypically stable cadmium-resistant (Cdr) variants. In contrast, treatment with any of three agents which alkylate proteins (N-ethylmaleimide, iodoacetate, or phenylmethyl-sulfonyl fluoride) was without effect. Similarly, treatment with 2-acetylaminofluorene (a pre-carcinogen) or with 12-O-tetradecanoylphorbol-13-acetate (a tumor promoter) did not result in an increase in Cdr variants. Initial studies indicate that in many variants the metallothionein-I gene, the metallothionein-II gene, or both have been activated. Thus the induction of cadmium resistance in Cds cells is a potentially useful system to explore the activation of quiescent genes by carcinogens.

Acetoxyacetylaminofluorene↗
PubMed1986

Interaction of the synthetic ultimate carcinogens, N-sulfonoxy- and N-acetoxy-2-acetylaminofluorene, and of enzymatically activated N-hydroxy-2-acetylaminofluorene with nucleophiles.

The interaction of four cellular nucleophiles with the putative ultimate carcinogens N-sulfonoxy-2-[ring-3H]acetylaminofluorene (N-sulfonoxy-2-AAF) and N-acetoxy-2-[ring-3H] acetylaminofluorene (N-acetoxy-2-AAF), and with N-hydroxy-2-[ring-3H]acetylaminofluorene (N-hydroxy-2-AAF) activated to the ultimate carcinogens by enzymatic sulfonation or transacetylation was determined. The adducts were isolated and adduct formation was quantified by isotope dilution. The order of nucleophilicity of the acceptors was guanosine greater than tRNA congruent to polyguanylic acid (poly G) greater than N-acetyl-L-methionine when N-sulfonoxy-2-AAF, N-acetoxy-2-AAF or N-hydroxy-2-AAF activated by transacetylation were the electrophiles. In the case of N-hydroxy-2-AAF activated by enzymatic sulfonation, the order of nucleophilicity was N-acetyl-L-methionine greater than guanosine congruent to tRNA greater than poly G. The increase in the reactivity of N-acetyl-L-methionine is hypothesized to be due to cytosolic enzyme(s) which facilitate transfer of the methionine residue from the nitrogen to carbon atoms 3 and 1 of the fluorene moiety. Of the two synthetic esters, N-sulfonoxy-2- AAF exhibited greater electrophilicity than N-acetoxy-2-AAF. The rate of adduct formation of N-sulfonoxy-2-AAF and of N-acetoxy-2-AAF with each nucleophile was a function of nucleophile concentration, indicative of a bimolecular reaction mechanism. The interaction is thought to involve attack of the nucleophile on the uncharged ultimate carcinogen, although interaction with an ion pair cannot be eliminated. The mutagenicity of N-sulfonoxy-2-AAF, N-acetoxy-2-AAF and of enzymatically activated N-hydroxy-2-AAF was evaluated by the Ames test. N-Sulfonoxy-2-AAF was virtually inactive, while N-acetoxy-2-AAF exhibited weak mutagenicity. N-Hydroxy-2-AAF activated by enzymatic sulfonation exhibited greater mutagenicity than synthetic N-sulfonoxy-2-AAF. The mutagenicity and reactivity of ultimate carcinogens derived from N-hydroxy-2-AAF by enzymatic activation do not necessarily coincide with the mutagenicity and reactivity of the synthetic ultimate carcinogens.

2-Acetylaminofluorene↗
PubMed1986

Peroxidase catalyzed aggregation of plasmid pBR322 DNA by benzidine metabolites in vitro.

The interaction of plasmid DNA and metabolites of benzidine produced by the action of horseradish peroxidase and hydrogen peroxide was investigated by a combination of agarose gel electrophoresis and autofluorography. Benzidine becomes irreversibly bound to the DNA to form a macromolecular structure that can no longer penetrate a 0.8% agarose gel. Other carcinogens such as o-dianisidine, o-tolidine and amino-fluorene also reacted in this way but N4-tetramethylbenzidine and the non-carcinogenic 3,5,3',5',tetramethylbenzidine did not.

Benzidines↗
PubMed1988

The influence of phenobarbital and butylated hydroxytoluene on the ploidy rate in rat hepatocarcinogenesis.

The effect of the 'promoters' phenobarbital (PB) and butylated hydroxytoluene (BHT) on the ploidy changes during hepatocarcinogenesis in rats was compared in a densitometric analysis of Feulgen-stained nuclei on paraffin-embedded tissue slices. The triphasic Gerlans protocol for liver-cancer induction was applied. Initiation with a single dose of diethylnitrosamine (DEN), and selection with 2-acetylamino-fluorene (2-AAF) combined with a proliferative stimulus (CCl4 administration), was followed by a treatment with PB or BHT for periods up to 22 weeks. Control animals received no treatment after the initiation and selection procedure. Despite intra- and inter-individual variations, an increase in the amount of 2N nuclei is found in the putative preneoplastic lesions of animals that received initiation and selection (I-S) and 3 weeks basal diet (BD). When the diet is supplemented with PB (after I-S), the increase of diploid nuclei starts earlier. At the time carcinoma arise (22 weeks PB treatment) a decrease in the frequency of 2N nuclei is found. BHT-treated animals which develop no carcinoma within the considered timespan, show a clear increased amount of 2N nuclei in the precancerous lesions only after 14 weeks treatment. It seems that there is a positive correlation between the outgrowth of putative preneoplastic foci and nodules in rat liver and an increase of diploid nuclei in these lesions. PB, as promoter used after initiation and selection, speeds up the development of carcinoma in rat liver, and therefore also the shift to diploidization in these rats starts earlier in comparison with I-S-treated rats. Although BHT does not promote liver carcinogenesis, an increase of diploid nuclei is also observed here during lesion formation. It may, therefore, be concluded that the phenomenon of diploidization is closely linked to and probably necessary for preneoplastic development, but that it is not an absolute indicator for neoplastic transformation.

Animals↗
PubMed1988

N- and O-deacetylation of N-acetoxy-N-arylacetamides by mammalian hepatic microsomes.

The present study demonstrates that hepatic microsomes from guinea pigs, rats, mice, hamsters, rabbits and dogs catalyze N-deacetylation of N-hydroxy-2-acetylaminofluorene (N-OH-AAF) and N-hydroxy-3,2'-dimethyl-4-acetylaminobiphenyl and O-deacetylation of N-acetoxy-2-acetylaminofluorene (N-AcO-AAF) and N-acetoxy-3,2'-dimethyl-4-acetylaminobiphenyl (N-AcO-DMAABP). Gel filtration resolves the solubilized guinea pig microsomal enzymes into two deacetylases. The larger molecular weight enzyme catalyzes N-deacetylation of N-OH-AAF, whereas the smaller one cannot. Both enzymes catalyze O-deacetylation of N-AcO-AAF and N-AcO-DMAABP, but the activity is mainly due to the larger enzyme. Guinea pig and rat liver microsomes also catalyze N-deacetylation of N-AcO-AAF resulting in the binding of 2-aminofluorene to nucleic acids, but the activities are much less than that of the O-deacetylation of N-AcO-AAF. Thus, the amino-fluorene-DNA adducts which have been found in intact cells treated with N-AcO-AAF may result directly from N-deacetylation or indirectly from N,O-acetyltransfer following O-deacetylation.

Acetamides↗
PubMed1988

In vitro binding of aflatoxin B1 and 2-acetylaminofluorene to rat, mouse and human hepatocyte DNA: the relationship of DNA binding to carcinogenicity.

DNA binding levels were determined and compared in cultured hepatocytes from male and female rats as well as other animal species following exposure to aflatoxin B1 (AFB1) or 2-acetylaminofluorene (2-AAF). When human, rat (both male and female) and mouse hepatocytes in primary culture were exposed to 2.0 X 10(-7) M [3H]AFB1 (sp. act. 2.63 microCi/nmol) for 24 h, male rat hepatocytes had the highest degree of [3H]AFB1-DNA binding (203 pmol/mg DNA) and human hepatocytes contained the next highest binding level (42 pmol/mg DNA). Hepatocytes from female rats contained 38 pmol/mg DNA while cultured mouse hepatocytes contained only 1.4 pmol/mg DNA. When the same dose of [3H]AFB1 was administered to the cultured male rat hepatocytes at 24 h, 48 h, 72 h and 1 week after seeding, and incubated for 24 h, the DNA binding levels were 189, 175, 76, 75 pmol/mg DNA respectively. In parallel experiments to the cultured male rat hepatocytes above, the AFB1-DNA binding levels in the cultured female hepatocytes were 42, 41, 37 and 34 pmol/mg DNA respectively. Human, male and female rat hepatocytes in primary culture were exposed to 5.2 X 10(-5) M 2-acetylamino[9-14C]fluorene (sp. act. 0.0094 microCi/nmol) for 24 h. It was determined that male rat hepatocytes contained the highest amount of radioactively labeled 2-AAF bound to their DNA (1.57 nmol/mg DNA), female rat hepatocytes contained 0.62 nmol/mg DNA and human hepatocytes contained 0.29 nmol/mg DNA. Results from our in vitro hepatocyte culture system correlate well with in vivo animal studies dealing with species and sex differences in DNA binding and carcinogenic susceptibility. This indicates that hepatocytes in vitro maintain many of the biological properties necessary for carcinogen response similar to liver cells in vivo. In addition, comparison of genotoxic effect in cultured hepatocytes from animals as well as humans may be useful in evaluating carcinogenic potential of xenobiotics in human liver.

2-Acetylaminofluorene↗
PubMed2000

Determination of polycyclic aromatic hydrocarbons in sediment using solid-phase microextraction with gas chromatography-mass spectrometry.

Manual solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS) is applied for the determination of polycyclic aromatic hydrocarbons (PAHs) from natural matrix through a distilled water medium. Seven of the 16 PAH standards (naphthalene, acenaphthene, fluorene, anthracene, fluoranthene, pyrene, benzo[a]anthracene) are spiked on a marine muddy sediment. The samples, containing PAHs in the range of 10-20 ppm, are then aged at room temperature more than 10 days before analysis. The influence of the matrix, SPME adsorption time, pH, salt content, and SPME adsorption temperature are investigated. The reproducibility of the technique is less than 13% (RDS) for the first 6 considered PAHs and 28% (RDS) for benzo(a)anthracene with a fiber containing a 100-micron poly dimethylsiloxane coating. Linearity extended in the range of 5-50 picograms for PAHs direct injection, 5-70 picograms for PAHs in water, and 1-170 picograms for PAHs in sediment. The detection limit is estimated less than 1 microgram/kg of dry sample for the first 6 considered PAHs in sediment and 1.5 micrograms/kg of dry sample for benzo(a)anthracene using the selected ion monitoring mode in GC-MS. The recoveries of the considered PAHs are evaluated.

Adsorption↗
PubMed1997

UvrAB activity at a damaged DNA site: is unpaired DNA present?

To study the activity of the Escherichia coli UvrA and UvrB nucleotide excision repair proteins during the formation of the pre-incision complex at a damaged DNA site, we used substrates with modifications around a single 2-(acetylamino)fluorene (AAF) lesion. Based on the release of AAF-containing oligonucleotides from a single-stranded DNA circle, we conclude that during interaction with our substrates UvrAB introduces changes in DNA which are localized at the lesion and are limited to 1-3 bp. Since these changes might include a denaturation of DNA at the lesion site and, consequently, a bubble structure might be present in a pre-incision complex, we studied incision activity of UvrABC excinuclease on substrates with 1-4 unpaired bases next to an AAF adduct. Opening more than one base on either or both sides of the lesion caused a significant decrease in the incision activity of UvrABC, but did not change the position of the incision sites. We conclude that the UvrAB action leading to a pre-incision complex does not include the formation of a bubble intermediate generated by extensive denaturation of base pairs.

2-Acetylaminofluorene↗
PubMed1997

The limited strand-separating activity of the UvrAB protein complex and its role in the recognition of DNA damage.

The recognition by Escherichia coli Uvr nucleotide excision repair proteins of a variety of lesions with diverse chemical structures and the presence of helicase activity in the UvrAB complex which can displace short oligonucleotides annealed to single-stranded DNA led to a model in which this activity moves UvrAB along undamaged DNA to damaged sites where the lesion blocks further translocation and the protein-DNA pre-incision complex is formed. To evaluate this mechanism for damage recognition, we constructed substrates with oligonucleotides of different lengths annealed to single-stranded DNA circles and placed a single 2-(acetylamino)fluorene (AAF) lesion either on the oligonucleotide or on the circle. For the substrates with no lesion, the UvrAB complex effectively displaced a 22-mer but not a 27-mer or longer fragments. The presence of AAF on the oligonucleotide significantly increased the release of the 27-mer but oligomers of 30 or longer were not separated. Placing the lesion on the circular strand did not block the release of the fragments. Instead, the releasing activity of UvrAB was stimulated and also depended on the length of the annealed oligonucleotide. These observations do not agree with the predictions of a damage recognition mechanism that depends on helicase-driven translocation. Most likely, the strand-separating activity of UvrAB is a consequence of local changes occurring during the formation of a DNA-protein pre-incision complex at the damaged site and is not due to translocation of the protein along undamaged DNA to locate a lesion.

2-Acetylaminofluorene↗
PubMed1988

Mouse lymphoma L5178Y thymidine kinase locus assay of 50 compounds.

Mutagenicity results are presented for 50 compounds tested in the mouse lymphoma TK+/(-)----TK-/- forward mutation assay. Test compounds were mostly from chemical classes not previously tested, to provide new information on the sensitivity of the assay; chemicals of low toxicity or thought to be non-carcinogenic and metabolic inhibitors, to indicate whether and under what conditions the assay can generate so-called false positive results. Twelve compounds that have been tested previously were included in this study to provide an indication of the reproducibility of the assay. Concordant results were obtained for nine of these, while disagreeing, positive results were seen with aniline, fluorene and pyrene. The following compounds belonging to the noncarcinogen category were positive at concentrations in the range 0.02-1 mol/l: dimethyl sulphoxide, EDTA, glucose, polyethyleneglycol, sodium chloride, sodium nitrite and urea. Measurements of the osmotic pressure indicated a lack of a simple relationship to mutagenic effects for these compounds. While the potent mutagenic/carcinogenic compounds tested gave greater than 4-fold increases in the mutation frequency, weak carcinogens or compounds not known to be carcinogenic that were positive in the assay gave increases of between 2- and 4-fold. Exceptions were aldehyde derivatives and chemicals that can lead to oxidative stress, which were detected with exaggerated sensitivity by the assay. Among the metabolic inhibitors tested, positive results were obtained with actinomycin D, cycloheximide, diethyl maleate, hydroxyurea and ouabain. Negative results were found with antimycin A. On the basis of the present results and previously published data it is concluded that a maximum limit for the test compound concentration can be set at 20 mmol/l and that testing to 20% total growth is adequate, with certain stipulations, to detect the mutagenic activity of test compounds. A similar analysis of the available test data shows that less than 4-fold increases in the mutation frequency have a lower predictivity for carcinogenicity.

Animals↗
PubMed1994

Marked antimutagenic potential of aqueous green tea extracts: mechanism of action.

In the present study aqueous extracts of green tea, at the concentrations customarily consumed by humans, were evaluated for their antimutagenic activity against major classes of dietary and occupational carcinogens. Green tea extracts caused a very marked and concentration-dependent inhibition of the Aroclor 1254-hepatic S9-mediated mutagenicity of heterocyclic amines (IQ and Glu-P-1) and polycyclic aromatic hydrocarbons (benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene) and of the isoniazid-induced S9-mediated mutagenicity of nitrosamines (nitrosopiperidine and nitrosopyrrolidine). Similar inhibition was seen in the mutagenicity of the two aromatic amines, namely 2-amino-fluorene and 2-aminoanthracene, whether Aroclor 1254-S9, isolated microsomes or cytosol served as the activation system. Finally, the mutagenicity of the direct-acting mutagens 9-aminoacridine and MNNG was also suppressed by green tea extracts, but the effect was less pronounced when compared with the indirect-acting mutagens. Green tea extracts caused a marked and concentration-dependent decrease in the O-dealkylation of methoxyresorufin, ethoxyresorufin and pentoxyresorufin. A similar inhibition of the NADPH-dependent reduction of cytochrome c was also observed. Following the termination of the microsomal metabolism of the various promutagens, incorporation of green tea extracts into the activation system resulted in a comparatively modest inhibition of their mutagenic response. It is concluded that aqueous extracts of green tea possess marked antimutagenic potential against a variety of important dietary and environmental mutagens. Two mechanisms appear to be responsible. The first involves a direct interaction between the reactive genotoxic species of the various promutagens and nucleophilic tea component(s) present in the aqueous extracts.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1983

Site-specific modification of the lactose operator with acetylaminofluorene.

We have synthesized the tetradecamer GAGCXGATAACAAG containing a part of the sequence of the lactose operator. A guanine base in the sequence is replaced by the adduct of the carcinogen 2-acetylaminofluorene with guanine. Under the standard conditions of de-protection, the fluorene moiety is lost, leaving behind a guanine oxidation product. New conditions of de-protection have been developed which allow the isolation of an oligonucleotide containing the adduct of 2-aminofluorene with guanine. The presence of the aminofluorene adduct greatly increases retention on reverse phase chromatography and produces a unique pattern of sequencing bands.

2-Acetylaminofluorene↗
PubMed1986

Time-resolved fluorometry: a sensitive method to quantify DNA-hybrids.

Europium and other lanthanides can be excitated with UV-radiation, whereafter the energy is released as fluorescence, delayed in time up to 1 ms after the excitation. Eu can be used as a sensitive label in biological assays. Here we report on the application of time-resolved fluorometry to detect nucleic acid hybrids. The probe DNA was tagged with a hapten, either a fluorene or a sulfone group. After hybridization the probe DNA was detected by a two-step immunological assay with the second antibody labelled with Eu. The method is quantitative with a detection limit of 0.3 pg of actual target regions of immobilized adenovirus genomic DNA. The label was also used in sandwich hybridization, which allowed analyzing nasopharyngeal mucus for the presence of adenovirus.

2-Acetylaminofluorene↗
PubMed1980

Infectivity and reconstitution of TMV RNA modified with N-acetoxy-2-acetylaminofluorene or benzol [a] pyrene 7,8-dihydrodiol 9,10 oxide.

TMV RNA was modified by two bulky carcinogens, N-acetoxy-2-acetylamino-fluorene (AAAF) and (+/-)-7beta, 8alpha- dihydroxy-9alpha, 10alpha-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene (BPDE), and the effects of such substituents on biological and physical properties was studied. For both types of modification, the loss of infectivity was directly proportional to the number of chemical modifications indicating that all modifications are lethal. Neither AAAF nor BPDE produced measurable mutations. Reconstitution of modified RNA with TMV protein was partially inhibited, but such inhibition occurred to similar extents with either carcinogen and a varying levels of modification. The data suggest that both types of substitution of TMV RNA generally permit the TMV coat protein to aggregate normally around the RNA, but that AAAF and BPDE may induce some conformational change in the initiation region that inhibits the initiation step.

2-Acetylaminofluorene↗
PubMed1981

Equilibrium binding of carcinogens and antitumor antibiotics to DNA: site selectivity, cooperativity, allosterism.

The equilibrium binding of the carcinogens N-hydroxy-N-acetyl-2-amino-fluorene (HAAF) and 4-nitroquinoline-1-oxide (NQO) to phi X174RF DNA have been studied by phase partition techniques. Both molecules bind in a cooperative manner with only a few carcinogen molecules binding to each phi X174RF DNA molecule. The binding data for both HAAF and NQO fit a model in which two carcinogens cluster into a small number of sites--four sites for HAAF and twelve sites for NQO. Phase partition techniques were also used to study the binding of actinomycin D to both calf thymus DNA and poly (dG-dC) . poly (dG-dC) at much lower r values than had been previously reported. These data exhibit humped Scatchard plots which are indicative of cooperative binding; the overall shape of the Scatchard plots are consistent with a model for drug induced allosteric transitions in the DNA structure. The cooperativity in the actinomycin D binding to calf thymus DNA increases with decreasing sodium chloride concentration, suggesting a role for DNA flexibility in allosteric binding.

2-Acetylaminofluorene↗
PubMed2002

Modulation of estrogen receptor-dependent reporter construct activation and G0/G1-S-phase transition by polycyclic aromatic hydrocarbons in human breast carcinoma MCF-7 cells.

It has been suggested that the estrogenicity of PAHs could contribute to their carcinogenic effects via increased tissue-specific cell proliferation. Both benzo[a]pyrene (BaP) and benz[a]anthracene (BaA) are known to weakly activate estrogen receptor (ER)-dependent reporter constructs. In this study, several other PAHs, including fluorene, fluoranthene, pyrene, chrysene, phenanthrene and anthracene, were found to act as very weak inducers of ER-mediated activity in the MCF-7 cell line stably transfected with a luciferase reporter gene. The effects of PAHs were time-dependent and they were not completely inhibited by antiestrogen ICI 182,780. In addition, BaP and BaA, as well as weakly estrogenic fluoranthene, significantly potentiated the maximum ER-mediated activity of 17beta-estradiol. Therefore, the effects of inhibitors of several types of protein kinases known to activate ERalpha in a ligand-independent manner were investigated. However, neither inhibitors nor inducers of extracellular signal-regulated kinases 1 and 2 (ERK1/2), phosphatidylinositol-3 kinase, protein kinase C, c-Src, or protein kinase A modified ER-mediated activity in this model. Neither estradiol nor BaA activated ERK1/2, two kinases suggested to play significant roles in ER signaling, suggesting that another kinase is involved in the observed phosphorylation of ERalpha. Similar to 17beta-estradiol, BaA stimulated G(0)/G(1)-S-phase transition in MCF-7 cells, which was fully suppressed by ICI 182,780. In conclusion, some PAHs can potentiate 17beta-estradiol-induced ER activation and stimulate cell cycle entry in vitro. However, their exact mode(s) of action and whether this phenomenon is of in vivo relevance remains to be elucidated.

Breast Neoplasms↗