کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2599797 1133228 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Fluoranthene enhances p53 expression and decreases mutagenesis induced by benzo[a]pyrene
موضوعات مرتبط
علوم زیستی و بیوفناوری علوم محیط زیست بهداشت، سم شناسی و جهش زایی
پیش نمایش صفحه اول مقاله
Fluoranthene enhances p53 expression and decreases mutagenesis induced by benzo[a]pyrene
چکیده انگلیسی

Fluoranthene (Fla) is the most abundant polycyclic aromatic hydrocarbon (PAH) in diesel particulate extracts. Benzo[a]pyrene (BaP) is genotoxic and is a prototype of PAH carcinogens. Fla's toxicity and mutagenicity are minor relative to BaP's. Our data showed that Fla enhanced BaP-induced p53 expression and promoted BaP-induced cell death. In contrast, Fla decreased BaP-induced mutagenesis. Fla had almost no influence on the cell cycle. However, the effect of cotreatment with BaP (1 μM) and Fla (10 μM) in regulating the cell cycle was greater than that of BaP (2 μM) alone. It is known that BaP activates the aryl hydrocarbon receptor (AhR), and, in turn, the AhR induces cytochrome P450 (Cyp)1a1 expression. The expression of Cyp1a1 corresponds well with the induction of apoptosis and mutagenesis by BaP. Fla did not activate the AhR or antagonize BaP's induction of AhR activity and Cyp1a1 expression. Therefore, the actions of Fla on BaP's toxicity were independent of the AhR signal and Cyp1a1. In summary, results indicated that Fla directs BaP-treated cells into death rather than mutagenesis, consequently preventing cells from being transformed. The novel cooperation between Fla and BaP provides valuable information for how to increase expression of the p53 tumor suppressor.


► Fluoranthene (Fla) promoted benzo[a]pyrene (BaP)-induced cell death.
► Fla synergistically enhanced BaP-induced p53 expression.
► Fla decreased BaP-induced mutagenesis.
► Actions of Fla on BaP's toxicity were independent of the aryl hydrocarbon receptor.
► Fla directs BaP-treated cells into death rather than mutagenesis.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Toxicology Letters - Volume 208, Issue 3, 5 February 2012, Pages 214–224
نویسندگان
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