In our work the antitumor and antimetastatic activities of
RNase A and
DNase I were studied using two murine models of pulmonary (
Lewis lung carcinoma) and liver (hepatoma A-1)
metastases. We found that intramuscular administration of
RNase A at the dose range of 0.1-50 µ g/kg retarded the primary
tumor growth by 20-40%, and this effect disappeared with the increase in
RNase A dose over 0.5 mg/kg.
DNase I showed no effect on the primary
tumor growth. The intramuscular administration of
RNase A (0.35-7 µ g/kg) or
DNase I (0.02-2.3 mg/kg) resulted in a considerable decrease in the
metastasis number into the lungs of animals with
Lewis lung carcinoma and a decrease of the hepatic index of animals with
hepatoma 1A. A histological analysis of the organs occupied by
metastases revealed that the administration of
RNase A and
DNase I induced
metastasis pathomorphism as manifested by the destruction of oncocytes, an increase in
necrosis and apoptosis foci in
metastases, and mononuclear infiltration. Our data indicated that
RNase A and
DNase I are highly promising as supplementary
therapeutics for the treatment of metastasizing
tumors.