The previous observation that the coadministration of a single dose of
thymidine with the 3'-chloroethylnitrosourea analog of
thymidine (3'-[3-(2-chloroethyl-3-nitrosoureido]-3'-
deoxythymidine, 3'-CTNU) to mice bearing the L1210 or
P388 leukemia enhanced the antitumor activity of 3'-CTNU, has led to a similar study of the potential effect on antitumor activity where
thymidine, 2'-
deoxyuridine, or 2'-
deoxycytidine is coadministered with 1,3-bis(2-chloroethyl)-1-nitrosourea. Three levels of 1,3-bis(2-chloroethyl)-1-nitrosourea (10, 15, and 20 mg/kg) were coadministered to mice bearing the
L1210 leukemia or the B16/F10
melanoma with each of the
deoxyribonucleosides (2 g/kg). There was not only an increase in average days of survival of those that perished, but also a marked increase in the number of greater than 60-day survivors. The present report is a result of a determination of whether the augmented anticancer activity produced by a single injection of
thymidine with 3'-CTNU was restricted to nitrosourea analogs of
thymidine. The present study reveals not only that the phenomena of enhanced anticancer activity by the coadministration of
thymidine can be extended to non-
thymidine-containing nitrosoureas, but also that the coadministration of
thymidine with 1,3-bis(2-chloroethyl)-1-nitrosourea produced an even more marked enhancement of antitumor activity than that previously observed when
thymidine was coadministered with 3'-CTNU.