Interspecies analysis of the chemopreventive efficacy of dietary alpha-difluoromethylornithine.
The anticarcinogenic efficacy of the polyamine biosynthesis inhibitor, alpha-difluoromethylornithine (DFMO), was assessed in three rodent models of human epithelial cancer. In DMBA-induced female, Sprague-Dawley rats, DMFO treatment (3.2 or 6.4 g/kg diet) for 180 days significantly inhibited mammary carcinogenesis and reduced tumor-related intercurrent mortality compared to untreated controls. In male, C57BL/6x DBA/2F1 mice induced with N-butyl-N(4-hydroxybutyl)nitrosamine (OH-BBN), DFMO treatment (2 or 4 g/kg diet) concurrent with the period of carcinogen administration significantly reduced the incidence and severity of urinary bladder carcinomas. In methylnitrosourea (MNU)-induced male Syrian golden hamsters, DFMO (3.2 g/kg diet) numerically reduced the incidence and size of tracheal carcinoma relative to untreated controls. DFMO-mediated toxicity was not evident in any of the animals on study, although a slight reduction in mean body weight gain was evident in rats and mice.
Ratko
T A
TA
Laboratory of Pathophysiology, IIT Research Institute, Chicago, Illinois 60616.
Detrisac
C J
CJ
Rao
K V
KV
Thomas
C F
CF
Kelloff
G J
GJ
Moon
R C
RC
D000818:Animals; D006224:Cricetinae; D004032:Diet; D000518:Eflornithine / Q000008:administration & dosage* / Q000627:therapeutic use; D005260:Female; D008325:Mammary Neoplasms, Experimental / Q000517:prevention & control; D008647:Mesocricetus; D051379:Mice; D008815:Mice, Inbred Strains; D009374:Neoplasms, Experimental / Q000517:prevention & control*; D051381:Rats; D011919:Rats, Inbred Strains; D013045:Species Specificity; D014134:Tracheal Neoplasms / Q000517:prevention & control; D001749:Urinary Bladder Neoplasms / Q000517:prevention & control
D000518:Eflornithine