N-Ethyloxycarbonylaminomehyl-
L-isoleucine (A-145), a novel antitumor
amino acid derivative, is an anti-
tumor agent effect in cases of Ehrlich
ascites rather than against Sarcoma-180. The chemotherapeutic index of
A-145 was 14.9 for Ehrlich
ascites carcinoma and 4.2 for
ascites Sarcoma-180. Experimental studies on ddy mice regarding the difference in susceptibility of these two tumor cell lines to
A-145 gave the following results. In in vivo experiments, the uptake of 14C-A-145 by Ehrlich
ascites carcinoma was greater than by Sarcoma-180, i. e. the uptake ratio of Ehrlich
ascites carcinoma/
Sarcoma-180 was 1.52 at 30 min and 2.7 at 24 hr after injection. In in vivo experiments, there was no remarkable difference between Ehrlich
ascites carcinoma and
Sarcoma 180 in the subcellular distribution of 14C-A-145, and the majority of the radioactivity taken up was distributed in nuclei and cytosol fractions. In in vitro experiments, the uptake of 14C-A-145 by both cell lines was found to be temperature sensitive,
glucose dependent, and decreased on addition of KCN, 2, 4-dinitrophenol or
iodoacetic acid. In in vitro experiments, competitive inhibition by
L-isoleucine on 14C-A-145 uptake into
tumor cells was observed in both cell lines, however, in vitro experiments, the inhibitory effect of
A-145 on cell growth in cultured Sarcoma-180 was not reversed by
L-isoleucine.