Abstract:
:The cytochrome P450 expression profile was determined in the MCF10A human breast epithelial cell line, as was the ability of this cell line to catalyze the bioactivation of the cooked food mutagen, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP). Using non-quantitative reverse transcription-polymerase chain reaction (RT-PCR), transcripts for CYP1B1, CYP2J2, CYP2R1, CYP2U1, CYP2W1, CYP4B1, CYP4F, CYP4V2, CYP4X1 and CYP4Z1 were detected in both sub-confluent and confluent MCF10A cells. By contrast, CYP1A2 mRNA was detected only in confluent MCF10A cells, while CYP1A1, CYP2S1 and CYP2F1 were detected predominantly or exclusively in sub-confluent cultures. 2,3,7,8-Tetrachlorodibenzo-p-dioxin treatment of confluent MCF10A cells markedly induced microsomal ethoxyresorufin O-deethylase activity and CYP1A1, CYP1A2 and CYP1B1 mRNA levels, as determined by real-time RT-PCR, while treatment with 10(-4)M PhIP had little effect on these P450 transcript levels. Treatment of confluent MCF10A cells with PhIP (10(-4)M) for 24, 48 or 72 h produced time-dependent increases in the amounts of DNA adducts, as measured by (32)P-post-labeling. These results indicate that multiple P450s, including those known to catalyze PhIP N-oxidation, are expressed in MCF10A cells, and that this non-neoplastic human breast epithelial cell line contains sufficient enzymatic machinery to support PhIP bioactivation and generate DNA damage.
journal_name
Chem Biol Interactjournal_title
Chemico-biological interactionsauthors
Thomas RD,Green MR,Wilson C,Weckle AL,Duanmu Z,Kocarek TA,Runge-Morris Mdoi
10.1016/j.cbi.2006.01.007subject
Has Abstractpub_date
2006-04-15 00:00:00pages
204-16issue
3eissn
0009-2797issn
1872-7786pii
S0009-2797(06)00017-2journal_volume
160pub_type
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