A family of epidermoid lung cancer models.

A family of epidermoid lung cancer models.
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表皮样肺癌模型家族。

DOI:
10.1016/s0003-4975(10)62323-5
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发表时间:
1984
期刊:
The Annals of thoracic surgery
影响因子:
--
通讯作者:
Teplitz,RL
Teplitz,RL
中科院分区:
--
文献类型:
--
作者:
Benfield,JR;Hammond,WG;Shors,EC;Paladugu,R;Pak,HY;Teplitz,RL

文献摘要

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本文提出了一种缓释植入方法,将分别浸渍2%(低剂量)和10%(高剂量)苯并[a]芘(BP)或甲基胆蒽(MCA)的硅橡胶圆筒插入金黄地鼠的中段支气管内。高剂量BP和MCA和低剂量MCA具有一级指数释放速率,高剂量BP的半衰期为40天,高剂量的MCA为30天,低剂量的MCA为165天。低剂量BP的释药速率为二次函数,半衰期为40天。在每种高剂量致癌物注入后4周,超过65%的仓鼠出现不典型的鳞状化生,而在低剂量致癌物注入后,不到30%的仓鼠出现非典型鳞状化生。在大剂量BP后约8周和低剂量BP后19周发现原位癌。在高剂量致癌剂注射后大约15到17周,%的动物患上了浸润性表皮样癌,而在低剂量致癌剂注射后,只有21%的动物患上了侵袭性表皮样癌。在接触高剂量致癌物25周后,超过85%的仓鼠患有浸润性表皮样癌;在低剂量致癌剂后,30%的仓鼠需要长达52周的时间才能发展为浸润性表皮样癌。图像分析显示,重度不典型鳞状化生细胞的核脱氧核糖核酸含量高于四倍体细胞(均值±标准差,3.77±1.4),而浸润性表皮样癌细胞为超六倍体(均值±标准差,6.48±3.6)。这些差异是显著的(p<0.05)。我们的结论是,表皮样肺癌的发育连续体现在可以在仓鼠身上以受控、可预测的方式复制。
A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[a]pyrene (BP) or methylcholanthrene (MCA) each at 2% (low dose) and 10% (high dose) concentrations, were inserted into the bronchus intermedius of hamsters. High-dose BP and MCA, and low-dose MCA had first-order exponential release rates: the half-time of release was 40 days for high-dose BP, 30 days for high-dose MCA, and 165 days for low-dose MCA. Release rate of low-dose BP was a second-order function: half-time of release was 40 days. Atypical squamous metaplasia was noted by 4 weeks in more than 65% of hamsters after insertion of each high-dose carcinogen but in less than 30% with the low-dose carcinogens. Carcinoma in situ was noted approximately 8 weeks after high-dose BP and 19 weeks after low-dose BP. At about 15 to 17 weeks after a high-dose carcinogen, 64% of animals had invasive epidermoid cancer, whereas after a low-dose carcinogen, only 21% did. After 25 weeks of exposure to a high-dose carcinogen, more than 85% of hamsters had invasive epidermoid cancer; up to 52 weeks were required for invasive epidermoid cancer to develop in 30% after a low-dose carcinogen. Measured by image analysis, nuclear deoxyribonucleic acid content of cells with severe atypical squamous metaplasia was greater than tetraploid (mean ± standard deviation [SD], 3.77 ± 1.4), whereas cells with invasive epidermoid cancer were suprahexaploid (mean ± SD, 6.48 ± 3.6). These differences are significant (p< 0.05). We conclude that the developmental continuum of epidermoid lung cancer can now be reproduced in controlled, predictable fashion in hamsters.