Enhanced malignant conversion of benign mouse skin tumors by cisplatin

Journal of the National Cancer Institute
H HenningsS H Yuspa

Abstract

The chemotherapeutic agent cisplatin, reported to be a complete carcinogen in rodents and a tumor initiator for mouse skin, was tested for activity to enhance the conversion of carcinogen-induced skin papillomas to carcinomas. Initiation of mouse skin by 7,12-dimethylbenz[a]anthracene followed by 12 weeks of promotion by 12-O-tetradecanoylphorbol-13-acetate produced seven to eight papillomas/mouse. Ten weekly injections of 100 micrograms of cisplatin into these papilloma-bearing mice induced a 2.3-fold enhancement of conversion relative to the spontaneous rate of 1.9%. Even a single exposure to cisplatin in tumor-bearing mice increased the carcinoma incidence to the same extent as 10 exposures to urethane, an agent previously shown to enhance malignant conversion. At the dose tested, cisplatin was inactive as a complete carcinogen or a tumor promoter. Cisplatin-DNA adducts, measured in samples from skin, liver, and kidneys, were persistent for at least 4 weeks after the last exposure to cisplatin. Thus cisplatin is a relatively potent inducer of the putative genotoxic changes required for conversion of skin tumors from a benign to a malignant phenotype. The activity of cisplatin in the initiation and malignant conversion stages...Continue Reading

Citations

May 10, 2003·Journal of Controlled Release : Official Journal of the Controlled Release Society·Jake A GilbertHenry F Edelhauser
Aug 29, 2009·Nature Protocols·Erika L AbelJohn DiGiovanni
Mar 7, 2006·International Journal of Gynecological Cancer : Official Journal of the International Gynecological Cancer Society·G PavlakisP Papasavas
Jul 3, 2007·Lung Cancer : Journal of the International Association for the Study of Lung Cancer·Akiko HisamotoMitsune Tanimoto
Oct 1, 1993·Gastroenterologia Japonica·T SattaH Takagi
Nov 1, 1994·The Journal of Investigative Dermatology·S H YuspaW C Weinberg

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