Neoplasms, oncogenicity studie

Chronic oncogenicity studies in animal models have led to methylene chloride being classified as an animal carcinogen. In treated mice, hepatocellular carcinomas and broncho/alveolar neoplasm have been reported to be significantly elevated over controls, while salivary gland sarcomas have been noted in male rats and increased incidences of leukemia and mammary adenomas found in female rats. Other lesions found in oncogenicity studies include mesotheliomas at multiple sites, mononuclear cell leukemias and hemangiomas. 

In a carcinogenicity study, rats and mice were given the liquid orally at two different dose levels, 5 days a week for 78 weeks." Both female and male test animals exhibited early mortality compared with untreated controls, and a variety of neoplasms were found in both treated animals and controls. Although rats of both sexes demonstrated a positive dose-related trend, no relationship was established between the dosage groups and the species, sex, type of neoplasm, or sites of occurrence. The lARC concluded that an evaluation of the carcinogenicity of 1,1,1-trichloroethane could not be made. In a subsequent study, rats exposed at 15 00 ppm 6 hours/day, 5 days/week for 2 years showed no oncogenic effects. ... 

The best demonstration that the loss of active normal p53 explains the oncogenic behavior of mutant p53 comes from studies in which a null mutation was introduced into the gene by homologous recombination in murine embryonic stem cells. Mice homozygous for the null allele appear to be normal but are prone to the development of a variety of neoplasms by 6 months of age. These observations suggest that a normal p53 gene is dispensable for embryonic development but that its absence predisposes the animal to neoplastic disease. 

Although tumor induction has mostly been documented in patients treated for cancer, long-term cyclophosphamide treatment for non-neoplastic conditions can also increase the incidence of certain neoplasms. Whether this oncogenic effect is a consequence of drug-induced chromosomal aberrations rather than immunosuppression is unclear. An increased incidence of bladder cancers, skin cancers, and myeloproliferative disorders was found in a 20-year follow-up study of 119 patients with rheumatoid arthritis, and a high dose of cyclophosphamide (mean total dose of 80 g) was the main susceptibihty factor (47). 

Satoh K, Sasano H, Shimos awa T, et al. An immunohistochemical study of the c-erbB-2 oncogene product in intraductal mucin-hypersecreting neoplasms and in ductal cell carcinomas of the pancreas. Cancer. 1993 72 51-56. 

There is a complex interplay in the oncogenic virus-host relationship that complicates the study of these viruses as well as the assessment of the risk associated with working with them. Many of the tumor viruses appear to be benign in their natural host, but are oncogenic in a heterologous species. Some viruses may not cause a neoplasm or tumor in their natural host species under normal conditions, but, at times, stress or immuno-... 

---