Glucksmann A, Cherry C P
Br J Cancer. 1970 Jun;24(2):333-51. doi: 10.1038/bjc.1970.39.
The effect of 5, 10, 20 or 40 weekly local applications of DMBA on the induction of cervico-vaginal epithelial and sarcomatous tumours and on that of squamous celled vulval neoplasms was investigated in intact and castrate rats. The threshold dose increases in the following order: epithelial cervico-vaginal tumours of castrates, followed by those in intacts and by squamous celled vulval tumours and lastly by sarcomas in castrates and intacts.The incidence of sarcomas levels off at about 25% after 20 doses in spayed rats, but increases to 70% with dose in intacts. All sarcomas appear between 200 and 400 days. The incidence of vulval neoplasms increases and the duration of the induction period decreases with dose.Significantly more cervico-vaginal epithelial tumours occur with 5 to 20 paintings than with further application of DMBA. Their peak value is 60% in castrates and 20% in intacts. Castration promotes the progression of vulval papillomas to carcinomas. The sensitivity to carcinogenic stimulation is thus tissue specific and also subject to modification by hormones.While epithelial tumours are multifocal and pass through well-defined intermediate stages (radication, papillomas, microcarcinomas) to full malignancy, the early stages of sarcoma formation are rarely detected and ill-defined. For epitheliomas and sarcomas "invasion" is a criterion of malignancy only if invading cells have acquired "xenoplasia", i.e. the ability to grow in new environments. This capacity increases progressively and its initial lack accounts for the discrepancy between the incidence of embolism and that of metastatic deposits.
在完整和去势大鼠中，研究了每周局部应用5次、10次、20次或40次二甲基苯蒽（DMBA）对宫颈阴道上皮肿瘤和肉瘤以及外阴鳞状细胞瘤诱导的影响。阈值剂量按以下顺序增加：去势大鼠的宫颈阴道上皮肿瘤，其次是完整大鼠的此类肿瘤、外阴鳞状细胞瘤，最后是去势和完整大鼠的肉瘤。在切除卵巢的大鼠中，20次给药后肉瘤的发生率稳定在约25%，但在完整大鼠中，肉瘤发生率随剂量增加至70%。所有肉瘤均出现在200至400天之间。外阴肿瘤的发生率随剂量增加，诱导期持续时间随剂量缩短。局部涂抹5至20次DMBA时发生的宫颈阴道上皮肿瘤明显多于继续涂抹DMBA时。其峰值在去势大鼠中为60%，在完整大鼠中为20%。去势促进外阴乳头状瘤向癌的进展。因此，对致癌刺激的敏感性具有组织特异性，且也受激素的影响。上皮肿瘤是多灶性的，经过明确的中间阶段（根除、乳头状瘤、微癌）发展为完全恶性，而肉瘤形成的早期阶段很少被检测到且定义不明确。对于上皮瘤和肉瘤，只有当侵袭细胞获得“异型增生”，即在新环境中生长的能力时，“侵袭”才是恶性的标准。这种能力逐渐增加，其最初的缺乏导致栓塞发生率与转移灶发生率之间的差异。
