The effects of increased numbers of carcinogenic treatments on the induction of cervico-vaginal and vulval tumours in intact and castrate rats.

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.