HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis.
HPV-16, tobacco-specific N-nitrosamine, and N-methyl-N'-nitro-N-nitrosoguanidine in oral carcinogenesis.
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发表时间：
1993-10
期刊：
影响因子：
11.2
通讯作者：
Myong Soo Kim;K. Shin;Jeong-Hwa Baek;H. Cherrick;No-Hee Park
中科院分区：
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作者：
Myong Soo Kim;K. Shin;Jeong-Hwa Baek;H. Cherrick;No-Hee Park
我们以前永生化人口腔角质形成细胞转染重组人乳头瘤病毒16型（HPV-16）DNA，并建立了两个细胞系。这些转染的细胞在形态上不同于正常细胞，含有完整的HPV-16 DNA，并表达许多病毒基因。与正常细胞相比，这些细胞含有较低水平的野生型p53蛋白和较高水平的c-myc mRNA。然而，它们仅在含有低水平钙的角质形成细胞生长培养基中增殖，并且在裸鼠中不具有致瘤性。将HPV-16永生化细胞系暴露于4-（甲基亚硝胺基）-1-（3-吡啶基）-1-丁酮或N-甲基-N '-硝基-N-亚硝基胍。分离出四个化学转化的细胞集落。这些细胞在含有生理水平钙的Dulbecco最低必需培养基中增殖良好。与永生对应物类似，它们包含整合的HPV-16序列，并且与正常细胞相比，野生型p53蛋白和DCC信息的水平较低。在化学转化的细胞中，从4-（甲基-亚硝胺）-1-（3-吡啶基）-1-丁酮暴露获得的两个集落在裸鼠中表现出增强的增殖能力，并转录了大量的HPV-16 E6/E7，表皮生长因子受体和c-myc基因相比，永生化的对应物。这些实验表明，口腔角质形成细胞的恶性转化可能是由“高危”HPV和烟草相关致癌物的连续联合作用引起的。
We previously immortalized human oral keratinocytes by transfection with recombinant human papillomavirus type 16 (HPV-16) DNA and established two cell lines. These transfected cells were morphologically different from the normal counterpart, contained intact HPV-16 DNA in an integrated form, and expressed numerous viral genes. These cells contained lower levels of wild-type p53 protein and higher levels of c-myc mRNAs compared to normal cells. However, they proliferated only in keratinocyte growth medium containing a low level of calcium and were not tumorigenic in nude mice. A HPV-16-immortalized cell line was exposed to either 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone or N-methyl-N'-nitro-N-nitrosoguanidine. Four chemically transformed cell colonies were isolated. These cells proliferated well in Dulbecco's minimum essential medium containing a physiological level of calcium. They contained, similar to the immortalized counterpart, integrated HPV-16 sequences and lower levels of both wild-type p53 protein and DCC messages compared to normal cells. Among the chemically transformed cells, two colonies obtained from 4-(methyl-nitrosamino)-1-(3-pyridyl)-1-butanone exposure demonstrated an enhanced proliferation capacity in nude mice and transcribed a substantially higher amount of HPV-16 E6/E7, epidermal growth factor receptors, and c-myc genes compared with the immortalized counterpart. These experiments indicate that malignant transformation of oral keratinocytes can be caused by a sequential combined effect of "high risk" HPV and tobacco-related carcinogens.