Induction of CYP1A1 and CYP1B1 and formation of carcinogen–DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene

Keshava, Channa; Divi, Rao L.; Whipkey, Diana L.; Frye, Bonnie; McCanlies, Erin C.; Kuo, Maryanne M.; Poirier, Miriam C.; Weston, Ainsley

doi:10.1016/j.canlet.2004.08.038

Cited by 29 publications

(23 citation statements)

References 40 publications

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“…* = P < 0.05 or less. 12 and 6 h incubation, respectively (Kemp et al, 2006;Keshava et al, 2005a). Such data are consistent with the B[a]P-mediated time-course induction of CYP1A1 and CYP1B1 reported herein; however, the ligand concentrations employed in those studies were much higher than ours (5 mM vs 100 nM), suggesting that the bovine mammary cells might be more sensitive than their human counterparts to CYP1 family enzyme up-regulation upon B[a]P exposure.…”

Section: Different Modulation Of Ahr Target Genes By Selected Ligandssupporting

confidence: 93%

Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands

et al. 2015

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Section: Different Modulation Of Ahr Target Genes By Selected Ligandssupporting

confidence: 93%

Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands

et al. 2015

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“…ATP binding cassette (ABC) transporter proteins, large membrane-bound protein play a major role in cancer drug resistance and physiologically provide general protection against hydrophobic xenobiotics (Sarkadi et al, 2006;Yeh et al, 1992). A wide interindividual variation of inducible drug metabolizing enzymes such as the cytochrome P450 isoenzymes CYP1A1 and CYP 1B1, which were shown to metabolize PAH is observed (Keshava et al, 2005). Cellular defense mechanisms against oxidative stress are affected by dietary factors.…”

Section: Discussionmentioning

confidence: 99%

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Baumeister

Reiter

Kleinsasser

et al. 2009

European Journal of Cancer Prevention

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Although epidemiological studies indicate cancer preventive effects of diets rich in fruit and vegetables, large clinical intervention studies conducted to evaluate dietary supplementation with micronutrients, mostly vitamins, showed disappointing results in large parts. In contrast, there is encouraging epidemiologic data indicating great chemopreventive potential of a large group of phytochemicals, namely polyphenols. This study shows the DNA protective effect epigallocatechin-3-gallate, a tea catechin, and one of the best-studied substances within this group, on carcinogen-induced DNA fragmentation in upper aerodigestive tract cells. Cell cultures from fresh oropharyngeal mucosa biopsies were preincubated with epigallocatechin-3-gallate in different concentrations before DNA damage was introduced with the metabolically activated carcinogen benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide or cigarette smoke condensate. Effects on resulting DNA fragmentation were measured using the alkaline single-cell microgel electrophoresis (comet assay). Epigallocatechin-3-gallate significantly reduced benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage by up to 51% (P<0.001). Fragmentation induced by cigarette smoke condensate could be lowered by 47% (P<0.001). Data suggest a cancer preventive potential of epigallocatechin-3-gallate as demonstrated on a subcellular level. An additional mechanism of tea catechin action is revealed by using a primary mucosa culture model.

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“…CYP1A1 and 1B1 are expressed in many tissues, including liver, lung, kidney, breast, and blood leukocytes. CYP1B1 is constitutively expressed in several steroidogenic and steroid responsive tissues, including breast, while CYP1A1 is mostly inducible (Berge et al, 2004; Keshava et al, 2005; Shimada et al, 2003; Spink et al, 1998; Whyatt et al, 1998). Both these enzymes are highly induced in tissues of experimental animals that are exposed to dioxins or PAHs (Shimada and Fujii-Kuriyama 2004; Whitlock et al, 1989; Whyatt et al, 1998) through the aryl-hydrocarbon receptor (AhR) pathway (Tsuchiya et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Chlorophyllin significantly reduces benzo[a]pyrene‐DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells

Keshava

Divi

Einem

et al. 2009

Environ and Mol Mutagen

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We hypothesized that chlorophyllin (CHLN) would reduce BP-DNA adduct levels. Using NHMECs exposed to 4 μM BP for 24 hr in the presence or absence of 5 μM CHLN, we measured BP-DNA adducts by chemiluminescence immunoassay (CIA). The protocol included the following experimental groups: BP alone, BP given simultaneously with CHLN (BP+CHLN) for 24 hr, CHLN given for 24 hr followed by BP for 24 hr (preCHLN, postBP), and CHLN given for 48 hr with BP added for the last 24 hr (preCHLN, postBP+CHLN). Incubation with CHLN decreased BPdG levels in all groups, with 87 % inhibition in the preCHLN, postBP+CHLN group. To examine metabolic mechanisms, we monitored expression by Affymetrix microarray (U133A), and found BP-induced up-regulation of CYP1A1 and CYP1B1 expression, as well as up-regulation of groups of interferoninducible, inflammation and signal transduction genes. Incubation of cells with CHLN and BP in any combination decreased expression of many of these genes. Using real time PCR (RT-PCR) the maximal inhibition of BP-induced gene expression, >85% for CYP1A1 and >70% for CYP1B1, was observed in the preCHLN, postBP+CHLN group. To explore the relationship between transcription and enzyme activity, the ethoxyresorufin-O-deethylase (EROD) assay was used to measure the combined CYP1A1 and CYP1B1 activities. BP exposure caused the EROD levels to double, compared to the unexposed controls. The CHLN-exposed groups all showed EROD levels similar to the unexposed controls. Therefore, the addition of CHLN to BP-exposed cells reduced BPdG formation and CYP1A1 and CYP1B1 expression, but EROD activity was not significantly reduced.

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Induction of CYP1A1 and CYP1B1 and formation of carcinogen–DNA adducts in normal human mammary epithelial cells treated with benzo[a]pyrene

Cited by 29 publications

References 40 publications

Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands

Constitutive expression of the AHR signaling pathway in a bovine mammary epithelial cell line and modulation by dioxin-like PCB and other AHR ligands

Epigallocatechin-3-gallate reduces DNA damage induced by benzo[a]pyrene diol epoxide and cigarette smoke condensate in human mucosa tissue cultures

Chlorophyllin significantly reduces benzo[a]pyrene‐DNA adduct formation and alters cytochrome P450 1A1 and 1B1 expression and EROD activity in normal human mammary epithelial cells

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