以苯并(a)芘處理人類口腔癌細胞株OC2 後p53 基因分子變化探討

Molecular characterization of mutation in the p53 gene of OC2 cells treated with Benzo(a)pyrene

廖光智(Kung-Chi Liao)

指導教授 ： 廖保鑫

中山醫學大學/口腔醫學院/口腔醫學研究所/碩士(2005年)

摘要

人類腫瘤約80%是由於與外界致癌物質接觸而引起的，根據
致癌物的性質可分為化學、生物和物理致癌物三大類。美國
著名流行病學者杜爾（Richard Doll）教授研究就曾指出，造
成癌症的因素中吸菸佔30％。葛應欽教授研究抽菸、喝酒與
吃檳榔三個習慣導致口腔癌之危險性增加一百二十三倍、其
中抽煙可增加十倍之危險性等，證明抽菸會造成口腔癌。香
菸中所含的化學物焦油（tar）長期被認為是造成癌症的初
始，實驗也顯示焦油之主要化學物質苯并(a)芘
[benzo(a)pyrene]能結合口腔細胞中之腫瘤抑制基因（tumor
suppressor gene）並且傷害它。p53 基因就是這類腫瘤抑制基
因，其主管作用是調控增殖的基因。
本篇研究的目的就是將致癌物質苯并(a)芘[B(a)P]處理人類
OC2 細胞株之p53 基因最易發生突變的核心（core）部份亦
即是外引子（exon）4 至外引子8，我們分別使用0、10、50、
100μM 的B(a)P 濃度，及1 天、7 天處理時間，同時考慮冷
凍保護劑二甲基亞楓(Dimethyl sulfoxide; DMSO)是否會造成
細胞的傷害等因素。結果顯示在培養基含有二甲基亞楓溶液
以濃度10μM 苯并(a)芘處理1 天後，p53 基因外引子5 密碼
組(codon) 161 GCC(丙氨酸)轉變為TCC(絲氨酸)，因而改變
p53 基因的結構，更因而喪失p53 基因的功能。我們的結論
是苯并(a)芘確實能造成p53 基因的突變，苯并(a)芘的濃度及
處理時間有待再研究。希望以後能進一步來探討其實際之影
響，以祈在預防與治療都能明顯的進展。

關鍵字

p53 基因 ； 苯并(a)芘 ； OC2 細胞株 ； 基因突變

並列摘要

About 80% of the human cancers cause by contact with the
carcinogens. Accroding to characterizing of the carcinogens, there
are 3 major stimuli：chemical, biologic, and physical. Professor
Richard Doll dictated cigarette smoking is an important factor to
cause cancer, its almost 30% in all cancer. Professor Ko YC
dictated also: one who have betel quid chew, cigarette smoking and
alcohol consumption will have 123 times high more risk than
non-use person.
A chemical in tobacco tar, which long has been the prime suspect in
the cancer connection, can cause certain genetic mutation in human
cells. The test-tube experiments shown that the tar chemical, benzo
（a）pyrene, can grab onto and damage a so-called tumor suppressor
gene in oral cells. p53 gene is one of these genes, and the gene
normally holds the reproduction of the oral cells.
The aim of this study, We use OC2 cells treated with benzo（a）
pyrene in differ concentrations (0, 10, 50, 100μM) and differ times
(1 day and 7 days) and we separatedthis OC2 cells into two groups
to contact DMSO or not, and We checked the core portion, exon 4
to exon 8, of the p53 gene. The result of these experiments
demonstrate that p53 mutation on exon 5 at codon 161[GCC (Ala) -> TCC (Ser) on the sample that B(a)P concentration is 10μM and
treated time is 1 day. The correlation between the mutation and the
concentration of B(a)P or treated time should be determined. We
hope this finding will be help to prevention of the oral cancer and so
as to cure the disease

並列關鍵字

p53 gene ； B(a)P ； OC2 cell line ； gene mutation

參考文獻

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