Dimers, trimers, and tetramers of bovine
ribonuclease A, obtained by lyophilization of the
enzyme from 40%
acetic acid solutions, were purified and isolated by
cation exchange chromatography. The two conformers constituting each aggregated species were assayed for their antitumor, aspermatogenic, or embryotoxic activities in comparison with monomeric
RNase A and bovine seminal
RNase, which is dimeric in nature. The antitumor action was tested in vitro on ML-2 (human
myeloid leukemia) and HL-60 (human myeloid cell line) cells and in vivo on the growth of human non-pigmented
melanoma (line UB900518) transplanted subcutaneously in nude mice.
RNase A oligomers display a definite antitumor activity that increases as a function of the size of the oligomers. On ML-2 and HL-60 cells, dimers and trimers generally show a lower activity than bovine seminal
RNase; the activity of tetramers, instead, is similar to or higher than that of the seminal
enzyme. The growth of human
melanoma in nude mice is inhibited by
RNase A oligomers in the order dimers < trimers < tetramers. The action of the two tetramers is very strong, blocking almost completely the growth of
melanoma.
RNase A dimers, trimers, and tetramers display aspermatogenic effects similar to those of bovine seminal
RNase, but, contrarily, they do not show any embryotoxic activity.