Ledwith B J, Storer R D, Prahalada S, Manam S, Leander K R, van Zwieten M J, Nichols W W, Bradley M O
Merck Sharp and Dohme Research Laboratories, West Point, Pennsylvania 19486.
Cancer Res. 1990 Sep 1;50(17):5245-9.
Determining to what degree chemicals and environmental agents contribute to the development of cancer would be materially enhanced by the ability to distinguish chemically induced tumors from those that arise spontaneously. Using DNA fingerprinting as an assay, we investigated whether somatic DNA rearrangements are more frequent in chemically induced mouse liver tumors than they are in spontaneous mouse liver tumors. Tumors were induced by a single i.p. injection of 12-day old male Crl:CD-1(ICR)BR (CD-1) mice with 20 nmol/g 7,12-dimethylbenz[a]-anthracene and were harvested 9 to 12 months after injection. Spontaneous tumors were obtained from 94- to 98-week old male CD-1 mice. We detected 8 rearrangements in 14 7,12-dimethylbenz[a]anthracene-induced tumors, which corresponds to a high rearrangement frequency of about 2% (of the minisatellite bands examined). Furthermore, 6 of these rearrangements included complete band losses which must have occurred early in tumor development. However, only 2 band changes were observed in 15 spontaneous tumors, and both changes were intensity shifts which may represent rearrangements that occurred later during tumor progression. Histological examination showed that the higher frequency of rearrangements in 7,12-dimethylbenz[a]anthracene-induced tumors versus spontaneous tumors was not related to differences in the degree of tumor progression or malignancy. Our results suggest that DNA fingerprinting may be a valuable assay for differentiating certain chemically induced tumors from spontaneous tumors.
如果能够区分化学诱导的肿瘤和自发产生的肿瘤，那么确定化学物质和环境因素在癌症发展过程中的作用程度将会得到实质性的提高。我们以DNA指纹图谱作为一种检测方法，研究了化学诱导的小鼠肝癌中体细胞DNA重排比自发小鼠肝癌中是否更频繁。给12日龄的雄性Crl:CD-1(ICR)BR（CD-1）小鼠腹腔注射一次20 nmol/g的7,12-二甲基苯并[a]蒽以诱导肿瘤形成，注射后9至12个月收获肿瘤。自发肿瘤取自94至98周龄的雄性CD-1小鼠。我们在14个7,12-二甲基苯并[a]蒽诱导的肿瘤中检测到8个重排，这对应于约2%（在所检测的小卫星条带中）的高重排频率。此外，这些重排中有6个包括完整条带的丢失，这肯定是在肿瘤发展早期发生的。然而，在15个自发肿瘤中仅观察到2个条带变化，且两个变化均为强度改变，这可能代表在肿瘤进展后期发生的重排。组织学检查表明，7,12-二甲基苯并[a]蒽诱导的肿瘤与自发肿瘤相比，重排频率较高与肿瘤进展程度或恶性程度的差异无关。我们的结果表明，DNA指纹图谱可能是区分某些化学诱导肿瘤和自发肿瘤的一种有价值的检测方法。
