CYP1C1 messenger RNA expression is inducible by benzo[a]pyrene in Fundulus heteroclitus embryos and adults.
CYP1C1 messenger RNA expression is inducible by benzo[a]pyrene in Fundulus heteroclitus embryos and adults.
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DOI：
10.1093/toxsci/kfl072
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发表时间：
2006-10
期刊：
影响因子：
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通讯作者：
Lu Wang;B. Scheffler;K. Willett
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文献类型：
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作者：
Lu Wang;B. Scheffler;K. Willett
CYP1C 是 P450 CYP1 家族的最新成员；然而，其生理意义、诱导物和代谢功能尚不清楚。克隆了异斜眼底 CYP1C1 互补 DNA 的两个全长等位基因。 529 个氨基酸的蛋白质与 Stenotomus chrysops CYP1C1 具有最高的氨基酸一致性（81%）。为了研究致癌物质苯并[a]芘 (BaP) 是否是 CYP1C1 诱导剂，我们使用实时 PCR 定量测量暴露于 BaP 的成鱼中 CYP1C1 和 CYP1A 信使 RNA (mRNA) 的组织和性别特异性表达。 CYP1C1 mRNA 表达在脑、脾、眼和性腺中高于 CYP1A，而 CYP1A 在胃肠道 (GI)、心脏、鳃和肝脏中较高。肾脏中两种 CYP1 的表达均等但较高。胃肠道、肝脏、鳃和眼睛的 CYP1 组成型表达存在性别差异。 BaP 暴露引起雌性和雄性心脏（31 倍和 17 倍）、鳃（7 倍和 4 倍）和肝脏（6 倍和 5 倍）中 CYP1C1 表达的诱导。胚胎 CYP1 表达在孵化后 2 周时达到最高，整个胚胎的 CYP1C1 mRNA 表达量是 CYP1A 的 3 至 15 倍。 BaP，10 微克/升，持续 10 天，在受精后 120 和 240 小时诱导这两种基因的诱导。我们的结果表明，除了 CYP1A 之外，硬骨鱼 CYP1C 也可由 BaP 诱导，具有广泛的组织分布，应进一步研究其在致癌物生物激活中的作用。
CYP1C is the newest member of the CYP1 family of P450s; however, its physiological significance, inducers, and metabolic functions are unknown. Two full-length alleles of Fundulus heteroclitus CYP1C1 complementary DNA were cloned. The 529 amino acid protein shared the highest amino acid identity with Stenotomus chrysops CYP1C1 (81%). To investigate whether the carcinogen benzo[a]pyrene (BaP) was a CYP1C1 inducer, we used real-time PCR to quantitatively measure tissue- and sex-specific expression of both CYP1C1 and CYP1A messenger RNAs (mRNAs) in BaP-exposed adult fish. CYP1C1 mRNA expression was constitutively higher than CYP1A in brain, spleen, eye, and gonad, while CYP1A was higher in gastrointestinal tract (GI), heart, gill, and liver. Kidney had equal but high expression of both CYP1s. There were sex differences in constitutive CYP1 expression in the GI, liver, gill, and eye. BaP exposure caused induction of CYP1C1 expression in female and male heart (31- and 17-fold), gill (seven- and four-fold), and liver (six- and five-fold), respectively. Embryo CYP1 expression was constitutively highest at 2 weeks posthatch, and whole embryos expressed 3- to 15-fold more CYP1C1 mRNA compared to CYP1A. BaP, 10 microg/l for 10 days, caused induction of both genes at 120 and 240 h postfertilization. Our results suggest that teleost CYP1C, in addition to CYP1A, is inducible by BaP, has a broad tissue distribution, and should be further investigated for its role in carcinogen bioactivation.