Benfield J R, Hammond W G, Shors E C, Paladugu R, Pak H Y, Teplitz R L
Ann Thorac Surg. 1984 Dec;38(6):627-32. doi: 10.1016/s0003-4975(10)62323-5.
A method of sustained release implantation has been developed whereby Silastic cylinders, impregnated with benzo[alpha]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 less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
已开发出一种缓释植入方法,即把分别含有2%(低剂量)和10%(高剂量)浓度苯并[a]芘(BP)或甲基胆蒽(MCA)的硅橡胶圆柱体插入仓鼠的中间支气管。高剂量BP和MCA以及低剂量MCA具有一级指数释放率:高剂量BP的释放半衰期为40天,高剂量MCA为30天,低剂量MCA为165天。低剂量BP的释放率是二级函数:释放半衰期为40天。在插入每种高剂量致癌物后4周,超过65%的仓鼠出现非典型鳞状化生,但低剂量致癌物组中该比例不到30%。高剂量BP后约8周出现原位癌,低剂量BP后19周出现。高剂量致癌物后约15至17周,64%的动物发生浸润性表皮样癌,而低剂量致癌物后只有21%发生。暴露于高剂量致癌物25周后,超过85%的仓鼠发生浸润性表皮样癌;低剂量致癌物后,30%的仓鼠发生浸润性表皮样癌需要长达52周。通过图像分析测量,重度非典型鳞状化生细胞的核脱氧核糖核酸含量大于四倍体(平均值±标准差[SD],3.77±1.4),而浸润性表皮样癌的细胞为超六倍体(平均值±SD,6.48±3.6)。这些差异具有统计学意义(p<0.05)。(摘要截断于250字)