Differential effect of over-expressing UGT1A1 and CYP1A1 on xenobiotic assault in MCF-7 cells.
Gene mutation has been considered as a major step of carcinogenesis. Some defective genes may induce spontaneous tumorigenesis, while others are required to interact with the environment to induce cancer. CYP1A1 and UGT1A1 are encoded for the respective phase I and II drug-metabolizing enzymes. Their expressions have been associated with breast cancer incidence in women, and some xenobiotics are substrates of these two enzymes. In the current study, cytochrome P450 (CYP) 1A1 and UDP-glucuronosyltransferase (UGT) 1A1 were over-expressed in the breast cancer MCF-7 cells, and potential interactions between these enzymes and estrogen or polycyclic aromatic hydrocarbon were evaluated. Compared with control cells (MCF-7(VEC)), reduced cell proliferation was seen in cells expressing UGT1A1 (MCF-7(UGT1A1)) under estradiol treatment. 7,12-Dimethylbenz[a]anthracene (DMBA) is an established breast cancer initiator in animal model. Over-expressing UGT1A1 reduced the binding of DMBA to DNA, and increased MCF-7(UGT1A1) intact cells under DMBA treatment was verified by comet assay. On the other hand, intensified DMBA binding and damages were observed in MCF-7(CYP1A1) cells. This study supported that UGT1A1 but not CYP1A1 expression could protect against xenobiotic assault.
Leung
Hau Y
HY
Food and Nutritional Sciences Programme, The Chinese University of Hong Kong, Shatin, NT, Hong Kong, China.
Wang
Yun
Y
Leung
Lai K
LK
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000378:metabolism / Q000633:toxicity; D001943:Breast Neoplasms / Q000201:enzymology* / Q000235:genetics; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D020552:Comet Assay; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004249:DNA Damage; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000378:metabolism / Q000633:toxicity; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D014453:Glucuronosyltransferase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D011960:Receptors, Estrogen / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation; D015262:Xenobiotics / Q000378:metabolism / Q000633:toxicity*; D000099148:UGT1A1 Enzyme
D015127:9,10-Dimethyl-1,2-benzanthracene; D019363:Cytochrome P-450 CYP1A1; D004247:DNA; D004958:Estradiol; D014453:Glucuronosyltransferase; D011960:Receptors, Estrogen; D015262:Xenobiotics; D000099148:UGT1A1 Enzyme