Role of estrogen receptor in regulation of polycyclic aromatic hydrocarbon metabolic activation in lung.
Epidemiological and biochemical studies have indicated that females may be at greater risk of smoking associated lung cancer compared with males. Among lung cancer patients, female smokers have been found to have higher levels of PAH-related DNA adducts and CYP1A1 gene expression in their normal lung tissue compared to male smokers. A possible role of steroid hormones in these sex differences via interactions between aryl hydrocarbon receptor and estrogen receptor mediated cellular effects has been suggested. In the present study the impact of the estrogen receptor (ERalpha) on CYP1A1 and CYP1B1 gene expression was studied in vitro in human bronchial epithelial cells. Transient transfection of the BEP2D cell line with ERalpha influenced neither constitutive expression of CYP1A1 or CYP1B1 nor induction of these genes by TCDD as measured by real-time RT-PCR. ERalpha had no effect on the constitutive or TCDD-induced enzymatic activity of CYP1A1 (EROD). We also studied the effect of steroid hormones on lung PAH metabolic activation in A/J mice. Intact and ovariectomized female mice were orally exposed to a single dose of benzo[a]pyrene. Ovariectomy did not influence the levels of either benzo[a]pyrene-derived protein or DNA adducts in the lung tissue measured by HPLC and 32P-postlabeling, respectively. In conclusion, the present data do not support the hypothesis of a role of estrogen or the ERalpha in regulating the metabolic activation of polycyclic aromatic hydrocarbons in lung.
Department of Toxicology, National Institute of Occupational Health, PO Box 8149 Dep, N-0033 Oslo, Norway.
Gisle
G
Berge
Steen
S
Mollerup
Steinar
S
ØVrebø
Alan
A
Hewer
David H
DH
Phillips
Einar
E
Eilertsen
Aage
A
Haugen
D000284:Administration, Oral; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases / Q000096:biosynthesis* / Q000494:pharmacology; D001564:Benzo(a)pyrene / Q000008:administration & dosage / Q000633:toxicity; D018929:Cell Culture Techniques; D019363:Cytochrome P-450 CYP1A1 / Q000096:biosynthesis* / Q000494:pharmacology; D065633:Cytochrome P-450 CYP1B1; D004273:DNA, Neoplasm / Q000032:analysis; D047628:Estrogen Receptor alpha; D004967:Estrogens / Q000494:pharmacology*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008175:Lung Neoplasms / Q000503:physiopathology*; D051379:Mice; D010052:Ovariectomy; D011084:Polycyclic Aromatic Hydrocarbons / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000502:physiology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012737:Sex Factors
D004273:DNA, Neoplasm; D047628:Estrogen Receptor alpha; D004967:Estrogens; D011084:Polycyclic Aromatic Hydrocarbons; D011960:Receptors, Estrogen; D001564:Benzo(a)pyrene; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585498:Cyp1b1 protein, mouse; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1