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.
Ohmori
T
T
Second Department of Pathology, Ehime University School of Medicine, Japan.
Okada
K
K
Tabei
R
R
Shibata
T
T
D000818:Animals; D002454:Cell Differentiation; D000518:Eflornithine / Q000008:administration & dosage*; D005260:Female; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000473:pathology; D009532:Nickel; D011073:Polyamines / Q000652:urine; D011700:Putrescine / Q000008:administration & dosage*; D051381:Rats; D011916:Rats, Inbred F344; D012509:Sarcoma / Q000139:chemically induced / Q000473:pathology; D016019:Survival Analysis
D011073:Polyamines; D009532:Nickel; D011700:Putrescine; D000518:Eflornithine