Mutagenesis and carcinogenesis induced by dibenzo[a,l]pyrene in the mouse oral cavity: a potential new model for oral cancer.
Mutagenesis and carcinogenesis induced by dibenzo[a,l]pyrene in the mouse oral cavity: a potential new model for oral cancer.
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DOI：
10.1002/ijc.26344
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发表时间：
2012-06-15
影响因子：
6.4
通讯作者：
El-Bayoumy, Karam
中科院分区：
文献类型：
--
作者：
Guttenplan, Joseph B.;Kosinska, Wieslawa;Zhao, Zhong-Lin;Chen, Kun-Ming;Aliaga, Cesar;DelTondo, Joseph;Cooper, Timothy;Sun, Yuan-Wan;Zhang, Shang-Min;Jiang, Kun;Bruggeman, Richard;Sharma, Arun K.;Amin, Shantu;Ahn, Kwangmi;El-Bayoumy, Karam
口腔癌是一种严重的疾病，在美国每年约有3万人受到影响。口腔癌有几种动物模型，但每种都有一定的缺点。作为一种新模型，我们研究了烟草烟雾致癌物二苯并[a，l]芘（DB[a,l]P）在B6C3F1 lacI和B6C3F1小鼠口腔中分别外用是否具有致突变性和致癌性。B6C3F1 lacI小鼠给予DB[a， 1]P (0,3,6,12 nmol) 3次/周。B6C3F1小鼠接受相同剂量和24 nmol。38周时，对lacI小鼠口腔组织进行诱变测定。高剂量组大鼠上黏膜和舌部突变体（MF）较单独给药组增加约2倍。这些增长在统计学上是显著的。将DB[a，l] p诱导的突变体与苯并[a]芘（BaP）诱导的口腔组织突变体进行比较。当灌胃给药时，BaP在许多组织中具有诱变性。与BaP相比，DB[a，l]P的突变谱与头颈癌中报道的p53突变更相似。在47周时，高剂量B6C3F1组中有31%的患者出现口腔鳞状细胞癌（OSCC）。肿瘤和发育不良组织中p53和COX-2蛋白升高。由于DB[a，l]P在口腔中诱导突变和肿瘤，并且在口腔组织中具有与人类OSCC中p53相似的突变谱，因此本文描述的治疗方案可能代表了一种新的相关口腔癌模型。
Cancer of the oral cavity is a serious disease, affecting about 30,000 individuals in US annually. There are several animal models of oral cancer, but each has certain disadvantages. As a new model, we investigated whether topical application of the tobacco smoke carcinogen, dibenzo[a,l]pyrene (DB[a,l]P) is mutagenic and carcinogenic in the oral cavity of the B6C3F1 lacI and B6C3F1 mouse, respectively. B6C3F1 lacI mice received DB[a,l]P (0, 3, 6, 12 nmol) 3× per week. B6C3F1 mice received the same doses and also 24 nmol. At 38 weeks mutagenesis was measured in oral tissues in lacI mice. For the high dose group, the mutant fraction (MF) in upper mucosa and tongue increased about twofold relative to that in vehicle-alone. The increases were statistically significant. The mutational profile in the DB[a,l]P-induced mutants was compared with that induced by benzo[a]pyrene (BaP) in oral tissue. BaP is mutagenic in many tissues when administered by gavage. The mutational profile for DB[a,l]P was more similar to that reported for p53 mutations in head and neck cancers than was that of BaP. At 47 weeks, oral squamous cell carcinomas (OSCC) were found in 31% of the high-dose B6C3F1 group. Elevations of p53 and COX-2 protein were observed in tumor and dysplastic tissue. As DB[a,l]P induces mutations and tumors in the oral cavity, and has a mutational profile in oral tissue similar to that found in p53 in human OSCC, the treatment protocol described here may represent a new and relevant model for cancer of the oral cavity.
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影响因子：
4.7
作者：
HIGGINBOTHAM, S;RAMAKRISHNA, NVS;CAVALIERI, EL
通讯作者：
CAVALIERI, EL
影响因子：
3.6
作者：
CAVALIERI, EL;ROGAN, EG;SALMASI, S
通讯作者：
SALMASI, S
DOI：
10.1073/pnas.92.22.10422
发表时间：
1995-10-24
影响因子：
11.1
作者：
CHAKRAVARTI, D;PELLING, JC;ROGAN, EG
通讯作者：
ROGAN, EG
影响因子：
3.6
作者：
Sharma, AK;Kumar, S;Amin, S
通讯作者：
Amin, S
影响因子：
4.7
作者：
Prahalad, AK;Ross, JA;Mass, MJ
通讯作者：
Mass, MJ