Mice were treated with daily
injections of
methylglyoxal bis(guanyl-
hydrazone) (
MGBG) without or with concurrent administration of 2-difluoromethylornithine (DFMO) in
drinking water for 15 days. Analysis of 10 different tissues for their
MGBG content during the treatment revealed little evidence for a tissue specific cumulative accumulation of the
drug given either alone or in combination with DFMO. On the contrary, tissue
MGBG levels tended to increase until the 4th to 7th day of the treatment, whereafter a gradual decline or a plateau was obvious in most tissues. The concomitant DFMO treatment produced a consistent elevation of tissue
MGBG concentrations in bone marrow cells and possibly also in intestinal tissue. In
L1210 leukemia-bearing DBA mice,
MGBG was most actively taken up by the ascitic
leukemia cells. A priming of the
tumor-bearing mice with DFMO for a few days before the start of
MGBG injections resulted in a strikingly enhanced accumulation of the latter
drug in the
leukemia cells and also in the spleen, which was apparently heavily infiltrated by
tumor cells. In liver, small intestine and in bone marrow cells of
tumor-bearing animals the concentration of
MGBG was not influenced by the DFMO treatment. In DBA mice without the L1210
tumor, DFMO only insignificantly increased the level of
MGBG in bone marrow cells whereas no increase was seen in the spleen, in contrast to the same organ obtained from
tumor-bearing mice. This combined treatment, in comparison with DFMO or
MGBG alone, also produced the best therapeutic response as revealed by marked reduction of the
tumor mass.