Metabolism of benzo[a]pyrene by cultured human hepatocytes from multiple donors.

Abstract:

:Primary hepatocyte cultures from six human donors were established and their abilities to metabolize the polycyclic aromatic hydrocarbon carcinogen benzo[a]pyrene (B[a]P) were examined. Cells from each donor were plated at similar densities (1 X 10(7) cells/100 mm dish). All cultures metabolized B[a]P to a significant extent (24-35 nmol in 24 h) and h.p.l.c. profiles of the organic solvent-soluble and glucuronidated B[a]P metabolites were obtained for all donors. The predominant extracellular organic solvent-soluble B[a]P metabolites were the 9,10- and 7,8-dihydrodiols, 9-hydroxy-B[a]P, and a mixture of tetrols, but the general ratios of these metabolites varied widely among the cells from different donors. In contrast, profiles were highly reproducible in cells from the same donor treated with B[a]P at either 8 or 24 h after initial plating. There was less variability in the amounts of specific B[a]P metabolites conjugated to glucuronic acid by cells from various donors. This variability could not be correlated with cell viability or overall levels of B[a]P metabolism. In addition, B[a]P metabolism by fresh and cryopreserved hepatocytes from the same donor was compared. While there was only a small reduction in the level of total B[a]P metabolism after cell freezing, there was a 3- to 5-fold increase in production of B[a]P-7,8-dihydrodiol, found both in the extracellular medium and as glucuronic acid conjugates, by the cryopreserved cells tested.

journal_name

Carcinogenesis

journal_title

Carcinogenesis

authors

Moore CJ,Gould MN

doi

10.1093/carcin/5.12.1577

subject

Has Abstract

pub_date

1984-12-01 00:00:00

pages

1577-82

issue

12

eissn

0143-3334

issn

1460-2180

journal_volume

5

pub_type

杂志文章
  • Role of the maternal environment in determining susceptibility to transplacentally induced chemical carcinogenesis in mouse fetuses.

    abstract::Treatment of pregnant mice with 3-methylcholanthrene (MC) causes lung and liver tumors in the offspring, the incidences of which are greatly influenced by the Ah locus regulated induction phenotype for aryl hydrocarbon hydroxylase activity (AHH) in both the mother and fetuses. In order to examine the biochemical and m...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/11.11.1979

    authors: Miller MS,Jones AB,Chauhan DP,Anderson LM

    更新日期:1990-11-01 00:00:00

  • Cyclin D1 gene polymorphism and susceptibility to lung cancer in a Chinese population.

    abstract::The objective was to study the relationship between cyclin D1 gene (CCND1) polymorphism and lung cancer in the Chinese population. Blood samples of 182 cases and 185 controls were collected from a hospital based case-control study. PCR-SSCP was used to examine the G/A polymorphism in exon 4 of CCND1. The results showe...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg035

    authors: Qiuling S,Yuxin Z,Suhua Z,Cheng X,Shuguang L,Fengsheng H

    更新日期:2003-09-01 00:00:00

  • Interaction of dietary fat and route of carcinogen administration on 1,2-dimethylhydrazine-induced colon tumorigenesis in rats.

    abstract::Since the results of an earlier study indicating no effect of dietary fat on dimethylhydrazine (DMH)-induced colon cancer in rats differed from those of other investigators, the present study was initiated to determine if the modulating effect of fat intake on colon tumorigenesis was dependent on the route of DMH admi...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.3.349

    authors: Locniskar M,Nauss KM,Kaufmann P,Newberne PM

    更新日期:1985-03-01 00:00:00

  • Susceptibility to prostate cancer: studies on interactions between UVR exposure and skin type.

    abstract::Recent studies have proposed that exposure to ultraviolet radiation (UVR) protects against development of some internal cancers including that in prostate. This effect may be mediated by UVR-induced cutaneous synthesis of vitamin D. It is also proposed that ability to pigment in response to UVR will influence suscepti...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgg021

    authors: Bodiwala D,Luscombe CJ,French ME,Liu S,Saxby MF,Jones PW,Ramachandran S,Fryer AA,Strange RC

    更新日期:2003-04-01 00:00:00

  • Genetic and epigenetic changes in rat preneoplastic liver tissue induced by 2-acetylaminofluorene.

    abstract::Genotoxic carcinogens, including 2-acetylaminofluorene (2-AAF), in addition to exerting their genotoxic effects, often cause a variety of non-genotoxic alterations in cells. It is believed that these non-genotoxic effects may be indispensable events in tumorigenesis; however, there is insufficient knowledge to clarify...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgm303

    authors: Bagnyukova TV,Tryndyak VP,Montgomery B,Churchwell MI,Karpf AR,James SR,Muskhelishvili L,Beland FA,Pogribny IP

    更新日期:2008-03-01 00:00:00

  • Comparative functional genomics for identifying models of human cancer.

    abstract::Genetically modified mice with overexpressed and/or deleted genes have been used extensively to model human cancer. However, it is uncertain as to what extent the mouse models reproduce the corresponding cancers in humans. We have compared the global gene expression patterns in human and mouse hepatocellular carcinoma...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi030

    authors: Lee JS,Grisham JW,Thorgeirsson SS

    更新日期:2005-06-01 00:00:00

  • Ellagic acid induces transcription of the rat glutathione S-transferase-Ya gene.

    abstract::Induction of glutathione S-transferase (GST) enzymes can increase detoxification of carcinogens and reduce carcinogen-induced mutagenesis and tumorigenesis. To determine if the anticarcinogen ellagic acid induces cellular enzymes which detoxify carcinogens, we examined the effect of ellagic acid on the expression of g...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/16.3.665

    authors: Barch DH,Rundhaugen LM,Pillay NS

    更新日期:1995-03-01 00:00:00

  • Steroid hormone receptor expression and proliferation in rat mammary gland carcinomas induced by 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine.

    abstract::2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) is a mammary gland carcinogen present in the human diet. Herein, the expression of estrogen receptor alpha (ERalpha), estrogen receptor beta (ER beta) and progesterone receptor (PR) was examined in mammary gland carcinomas induced by PhIP in female Sprague-Dawley ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi013

    authors: Qiu C,Shan L,Yu M,Snyderwine EG

    更新日期:2005-04-01 00:00:00

  • CYP1A1 Ile462Val and MPO G-463A interact to increase risk of adenocarcinoma but not squamous cell carcinoma of the lung.

    abstract::Common polymorphisms in genes encoding phase I and phase II enzymes are considered to modify lung cancer risk due to changes in enzyme activity. Candidates include genetic variants of glutathione S-transferases (GSTM1, GSTT1 and GSTP1) and myeloperoxidase (MPO). We performed a large case-control study of these candida...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi227

    authors: Larsen JE,Colosimo ML,Yang IA,Bowman R,Zimmerman PV,Fong KM

    更新日期:2006-03-01 00:00:00

  • Ha-rasVal12 but not p53Ser247 leads to a significant neoplastic transformation rate of the putative rat liver stem cells (oval cell).

    abstract::In order to test the controversially discussed hypothesis that oval cells are part of a liver stem cell compartment and can give rise to cholangiocellular as well as hepatocellular carcinomas in the course of liver carcinogenesis, we transfected an oval cell line established in our laboratory with an oncogenically act...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/17.12.2635

    authors: Becker R,Lüthgens B,Oesch F,Dienes HP,Steinberg P

    更新日期:1996-12-01 00:00:00

  • Differential effects of resveratrol on androgen-responsive LNCaP human prostate cancer cells in vitro and in vivo.

    abstract::Resveratrol is a phytochemical that has been under consideration for use as a prostate cancer chemopreventive agent. However, the efficacy, as well as the mechanisms of action of resveratrol on prostate cancer prevention, remains largely unknown. This study seeks to address these questions and examine the cancer preve...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn131

    authors: Wang TT,Hudson TS,Wang TC,Remsberg CM,Davies NM,Takahashi Y,Kim YS,Seifried H,Vinyard BT,Perkins SN,Hursting SD

    更新日期:2008-10-01 00:00:00

  • In vitro enzymatic recognition of DNA modified by O,O'-diacetyl or O-acetyl derivatives of the carcinogen 4-hydroxyaminoquinoline-1-oxide.

    abstract::Purified DNA was modified in vitro by 3H-labelled O-acetyl or O,O'-diacetyl-4-hydroxyaminoquinoline-1-oxide (Ac4HAQO or di Ac-4HAQO). It was then subjected to the action of the single-stranded DNA specific nuclease S1 and the digested fractions were analysed. For both types of modified DNA, the release of non-modified...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/3.4.435

    authors: Galiègue S,Bailleul B,Loucheux-Lefebvre MH,Laval J

    更新日期:1982-01-01 00:00:00

  • Heterocyclic aromatic amines induce DNA strand breaks and cell transformation.

    abstract::Heterocyclic aromatic amines (HAAs), formed during the cooking of foods, are known to induce tumours in rodent bioassays and may thus contribute to human cancer risk. We tested six HAAs in a morphological transformation assay and in three in vitro genotoxicity assays. The morphological transforming abilities of HAAs w...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.4.545

    authors: Pfau W,Martin FL,Cole KJ,Venitt S,Phillips DH,Grover PL,Marquardt H

    更新日期:1999-04-01 00:00:00

  • Polymorphisms in the MTHFR and VDR genes and skin cancer risk.

    abstract::Folate and vitamin D have been shown to be influenced by ultraviolet (UV) radiation. UVA radiation can break down plasma folate, whereas vitamin D can be synthesized in UVB-exposed skin. Folate metabolism is involved in DNA synthesis and repair, and vitamin D processes anti-proliferative effects. The functions of both...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgl156

    authors: Han J,Colditz GA,Hunter DJ

    更新日期:2007-02-01 00:00:00

  • Role for EPS8 in squamous carcinogenesis.

    abstract::We have investigated the role of the signaling intermediate, EPS8, in tumor progression using a model system and in vivo. HN4 primary tumor cells express low levels of EPS8, similar to normal keratinocytes, and show minimal invasion in vitro in response to epidermal growth factor, whereas HN12 cells express high level...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn252

    authors: Wang H,Patel V,Miyazaki H,Gutkind JS,Yeudall WA

    更新日期:2009-01-01 00:00:00

  • Induction of high incidence of mammary tumour in female Noble rats with a combination of 17beta-oestradiol and testosterone.

    abstract::Breast cancer is the most common cancer and the second most frequent cause of cancer death in women. Despite extensive research, the precise mechanisms of breast carcinogenesis remain unclear. One of the reasons for this is due, at least in part, to a lack of a suitable animal model which can closely mimic the breast ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/20.6.1069

    authors: Xie B,Tsao SW,Wong YC

    更新日期:1999-06-01 00:00:00

  • Organochlorine-mediated potentiation of the general coactivator p300 through p38 mitogen-activated protein kinase.

    abstract::The activity of nuclear transcription factors is often regulated by specific kinase-signaling pathways. We have previously shown that the organochlorine pesticide dichlorodiphenyltrichloroethane (DDT) stimulates activator protein-1 activity through the p38 mitogen-activated protein kinase (MAPK). Here, we show that DD...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgn213

    authors: Bratton MR,Frigo DE,Vigh-Conrad KA,Fan D,Wadsworth S,McLachlan JA,Burow ME

    更新日期:2009-01-01 00:00:00

  • Cytochrome P450-dependent metabolism and mutagenicity of 15,16-dihydro-11-methylcyclopenta[a]phenanthren-17-one and their implications in its carcinogenicity.

    abstract::Methylation of the non-carcinogen 15,16-dihydrocyclopenta[a]phenanthren-17-one (CPP-17-one) at the bay region to form 11-CH3-CPP-17-one confers carcinogenic potential. In the present study we have investigated the in vitro metabolism and mutagenicity of the methylated compound by hepatic microsomal preparations from r...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/14.9.1783

    authors: Boyd GW,Young RJ,Harvey RG,Coombs MM,Ioannides C

    更新日期:1993-09-01 00:00:00

  • Activation of trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene to genotoxic metabolites by rat and human cytochromes P450.

    abstract::In order to address the hypothesis that 6-aminochrysene (6-AC) is converted to genotoxic products by cytochrome P450 enzymes via two activation pathways (N-hydroxylation and epoxidation), the activation of 6-AC and trans-1,2-dihydro-1,2-dihydroxy-6-aminochrysene (6-AC-diol) to genotoxic metabolites was examined in rat...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.3.465

    authors: Yamazaki H,Mimura M,Oda Y,Gonzalez FJ,el-Bayoumy K,Chae YH,Guengerich FP,Shimada T

    更新日期:1994-03-01 00:00:00

  • Inhibition of growth factor-induced Ras signaling in vascular endothelial cells and angiogenesis by 3,3'-diindolylmethane.

    abstract::3,3'-Diindolylmethane (DIM), an indole derivative produced on consumption of broccoli and other cruciferous vegetables, has been shown to have multiple anticancer effects in both in vivo and in vitro models. The present study was carried out to clarify the mechanism of DIM's antiangiogenic activity. We found that DIM ...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi230

    authors: Chang X,Firestone GL,Bjeldanes LF

    更新日期:2006-03-01 00:00:00

  • Synergistic anti-breast cancer effect of a combined treatment with the methyl donor S-adenosyl methionine and the DNA methylation inhibitor 5-aza-2'-deoxycytidine.

    abstract::DNA-demethylating agents activate tumor suppressor genes that are silenced by DNA methylation in cancer and are therefore emerging as a novel approach to cancer therapy. 5-azacytidine (VIDAZA), the first representative of this class of drugs was approved for treatment of myelodysplastic syndromes and is currently bein...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgt284

    authors: Chik F,Machnes Z,Szyf M

    更新日期:2014-01-01 00:00:00

  • A study of multiple biomarkers in coke oven workers--a cross-sectional study in China.

    abstract::We conducted a cross-sectional molecular epidemiological study of coke oven workers exposed to the established carcinogen polycyclic aromatic hydrocarbons (PAHs) to evaluate the relationships between both traditional 'exposure markers' and a series of biomarkers, including urinary 1-hydroxypyrene as a marker of intern...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/19.11.1963

    authors: Pan G,Hanaoka T,Yamano Y,Hara K,Ichiba M,Wang Y,Zhang J,Feng Y,Shujuan Z,Guan D,Gao G,Liu N,Takahashi K

    更新日期:1998-11-01 00:00:00

  • Induction of the aromatic hydrocarbon receptor by trans-4-acetylaminostilbene in rat liver. Comparison with other aromatic amines.

    abstract::The effect of the aromatic amines 2-acetylaminofluorene (AAF), 2-acetylaminophenanthrene (AAP) and trans-4-acetylaminostilbene (AAS) on the rat hepatic aromatic hydrocarbon (Ah) receptor level was studied. 3-Methylcholanthrene (MC), as a known receptor ligand, was used as a control. The complete liver carcinogen AAF a...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/8.7.1021

    authors: Göttlicher M,Cikryt P

    更新日期:1987-07-01 00:00:00

  • DNA adducts formed from the probable proximate carcinogen, N-hydroxy-3,2' -dimethyl-4-aminobiphenyl, by acid catalysis or S-acetyl coenzyme A-dependent enzymatic esterification.

    abstract::The arylamine carcinogen 3,2'-dimethyl-4-aminobiphenyl (DMABP) has been proposed to be metabolically activated to DNA-binding derivatives through the formation of an N-hydroxy intermediate. In this study, the subsequent activation of N-hydroxy-DMABP through acid catalysis or enzymatic esterification was examined. [Rin...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/6.2.251

    authors: Flammang TJ,Westra JG,Kadlubar FF,Beland FA

    更新日期:1985-02-01 00:00:00

  • The yin and yang of nitric oxide in cancer progression.

    abstract::Nitric oxide (NO) is a short-lived, pleiotropic molecule that affects numerous critical functions in the body. Presently, there are markedly conflicting findings in the literature regarding NO and its role in carcinogenesis and tumor progression. NO has been shown to have dichotomous effects on cellular proliferation,...

    journal_title:Carcinogenesis

    pub_type: 杂志文章,评审

    doi:10.1093/carcin/bgt034

    authors: Burke AJ,Sullivan FJ,Giles FJ,Glynn SA

    更新日期:2013-03-01 00:00:00

  • Hepatic and extrahepatic bioactivation and GSH conjugation of aflatoxin B1 in sheep.

    abstract::Whole-body autoradiography of [3H]aflatoxin B1 ([3H]AFB1) in lamb showed a localization of bound labelling, in addition to the liver, in the nasal olfactory and respiratory mucosa, in the mucosa of the nasopharynx, pharynx, oesophagus, larynx, trachea, bronchi and bronchioles and in the palpebral and bulbar conjunctiv...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/15.5.947

    authors: Larsson P,Busk L,Tjälve H

    更新日期:1994-05-01 00:00:00

  • Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer.

    abstract::Lack of functional telomeres can cause chromosomal aberrations. This type of genetic instability may promote tumorigenesis. We have investigated the association between mean telomere length in buccal cells (assessed with quantitative real-time PCR) and bladder cancer risk in a case-control study. Patients with bladder...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgi063

    authors: Broberg K,Björk J,Paulsson K,Höglund M,Albin M

    更新日期:2005-07-01 00:00:00

  • Epigenetic modulation combined with PD-1/PD-L1 blockade enhances immunotherapy based on MAGE-A11 antigen-specific CD8+T cells against esophageal carcinoma.

    abstract::Cancer testis antigens (CTAs) are promising targets for T cell-based immunotherapy and studies have shown that certain CT genes are epigenetically depressed in cancer cells through DNA demethylation. Melanoma-associated antigen A11 (MAGE-A11) is a CTA that is frequently expressed in esophageal cancer and is correlated...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa057

    authors: Wu Y,Sang M,Liu F,Zhang J,Li W,Li Z,Gu L,Zheng Y,Li J,Shan B

    更新日期:2020-07-14 00:00:00

  • Candidate gene association analysis of acute lymphoblastic leukemia identifies new susceptibility locus at 11p15 (LMO1).

    abstract::To determine the contribution of susceptibility loci in explaining the genetic basis of acute lymphoblastic leukemia (ALL), we genotyped 29 high-potential candidate genes with 672 tagged single-nucleotide polymorphisms (SNPs) in a sample (163 cases and 251 healthy controls) of Caucasian children. Fifty SNPs in 15 gene...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgr091

    authors: Beuten J,Gelfond JA,Piwkham D,Pollock BH,Winick NJ,Collier AB 3rd,Tomlinson GE

    更新日期:2011-09-01 00:00:00

  • Enhanced communication of IARC Monograph findings to better achieve public health outcomes.

    abstract::IARC Monographs are globally-recognized assessments of carcinogenicity published by International Agency for Research on Cancer and directed to national authorities as a contribution to public health. Currently, though not constraining the scope of studies examined, Monographs are declared to involve only hazard ident...

    journal_title:Carcinogenesis

    pub_type: 杂志文章

    doi:10.1093/carcin/bgaa129

    authors: Stewart BW

    更新日期:2020-12-01 00:00:00