Effects on tumor induction, growth, metastasis and histology of concurrent administration of putrescine and its metabolizing inhibitor alpha-difluoromethylornithine in nickel tumorigenesis in soft tissue.

The effects of putrescine and the inhibitor of its biosynthesis alpha-difluoromethylornithine (DFMO) on nickel tumorigenesis in soft tissue was studied. Three groups of female F-344 rats were injected i.m. with 10 mg of nickel subsulfide (NiSS) in the right hind leg, after which one group was administered 200 mg/kg body wt of putrescine (i.p.) once a week, and one group was administered 0.2% DFMO in the drinking water for 32 weeks until termination. The DFMO-treated group exhibited longer tumor induction time, lower tumor growth rate and significantly lower metastatic rate, whereas the putrescine-treated group exhibited a temporarily higher tumor growth rate than the NiSS-only group. Histologically, the putrescine-treated group and especially the DFMO-treated group frequently exhibited differentiated sarcomas but the NiSS-only group exhibited anaplastic sarcomas. The present study demonstrated that long-term administration of DFMO has an inhibitory effect on tumors and metastasis, and induces differentiation of tumor cells from anaplastic round cells to well-differentiated pleomorphic cells in NiSS tumorigenesis in soft tissue.