Reddy A L, Fialkow P J
Department of Medicine, University of Washington, Seattle 98195.
Carcinogenesis. 1988 May;9(5):751-4. doi: 10.1093/carcin/9.5.751.
We examined the effects of initiation with different doses of 7,12-dimethylbenz[a]anthracene (DMBA) on two-stage skin carcinogenesis in BALB/c mice. The induction of skin papillomas and their sequential tumor progression were followed by determination of locations of the tumors on the back of each mouse, by histological evaluation and by determining the phosphoglycerate kinase (PGK) phenotypes of neoplasms. Three doses of DMBA were tested, 20.0, 2.0 and 0.2 micrograms. Lowering the dose of DMBA initiation prolonged tumor latency and reduced tumor susceptibility and frequency. All of the papillomas that developed with the lowest dose of DMBA initiation were found to be clonal by PGK analysis and each of them was promoter dependent; termination of TPA promotion led to its regression. The 0.2-micrograms DMBA initiation dose also reduced to zero the delayed promoter-independent papillomas and the frequency of papillomas changing their PGK phenotype during tumor progression. Thus, these studies provide evidence that the carcinogen not only causes initiation in mouse skin epidermal cells but also that the dose of carcinogen strongly influences the mode of growth of the initiated cells to papillomas and the progression of these tumors.
我们研究了用不同剂量的7,12-二甲基苯并[a]蒽（DMBA）启动对BALB/c小鼠两阶段皮肤致癌作用的影响。通过确定每只小鼠背部肿瘤的位置、组织学评估以及测定肿瘤的磷酸甘油酸激酶（PGK）表型，来跟踪皮肤乳头瘤的诱导及其连续的肿瘤进展情况。测试了三种剂量的DMBA，分别为20.0、2.0和0.2微克。降低DMBA启动剂量可延长肿瘤潜伏期，降低肿瘤易感性和发生率。通过PGK分析发现，以最低剂量DMBA启动所产生的所有乳头瘤都是克隆性的，并且它们中的每一个都依赖于启动子；终止TPA启动会导致其消退。0.2微克的DMBA启动剂量还使延迟的非启动子依赖性乳头瘤以及在肿瘤进展过程中改变其PGK表型的乳头瘤的发生率降至零。因此，这些研究提供了证据，证明致癌物不仅会在小鼠皮肤表皮细胞中引发致癌作用，而且致癌物的剂量还会强烈影响引发细胞发展为乳头瘤的生长模式以及这些肿瘤的进展。
