The effects of
DL-alpha-difluoromethylornithine (DFMO), a specific, irreversible inhibitor of
ornithine decarboxylase (ODC), on
tumors induced in the muscle of C57BL mice by Lewis lung (LL)
carcinoma cells and on the development of lung
metastases have been investigated. ODC activity and
putrescine,
spermidine and
spermine concentrations were increased both during the early phase of development of the primary LL
tumor and in the lung coinciding with the development of
metastases. Oral treatment with DFMO (2% aqueous
solution as sole drinking fluid, equivalent to 4 g DFMO/kg/day) decreased markedly the ODC activity and the
putrescine and
spermidine concentrations of the primary
tumor, and stimulated
S-adenosyl-L-methionine decarboxylase activity. ODC activity and
putrescine and
spermidine concentrations were similarly markedly reduced in the metastatic lung by DFMO treatment. By comparison with untreated controls, DFMO treatment from day 1 after inoculation resulted in an 81% decrease in
tumor size and a 92% reduction of lung
metastases by day 20 and prolonged the mean survival time from 20.2 to 28.8 days. The same treatment regimen started 8 days after
tumor inoculation resulted in a 52% inhibition of
tumor growth and an 82% reduction of lung
metastases, and prolonged the mean survival time to 24.9 days. The clear antitumoral effects obtained with DFMO on this animal metastatic
cancer indicate its potential value in the treatment of
metastases in humans.