Action of miracil d and related compounds on dna and rna synthesis in regenerating liver and hepatomas

Miracil D (1‐diethylaminoethylamino‐4‐methyl‐10‐thiaxanthenone) caused a large and prolonged inhibition of thymidine‐³H incorporation into DNA of regenerating rat liver. A similar effect was observed with hycanthone and a desethyl derivative of Miracil D, which also complexes with DNA, but not with a noncomplexing congener bearing a methyl substituent on the proximal nitrogen of the dialkylaminoalkylamino side chain. Miracil D caused a less marked inhibition of orotate‐³H incorporation into RNA at 6 and 24 h after partial hepatectomy. Administration of Miracil D 16 h before measurement of DNA synthesis had a marked inhibitory effect on three slowly growing hepatomas (9618A, 47C and 7787) but had little or no effect on three rapidly growing hepatomas (3924A, 5123tc and 7777). RNA synthesis was not inhibited in hepatoma 7777 under these conditions, but a small, though significant, inhibition of tumor DNA synthesis was observed in rats subjected to partial hepatectomy. The data suggested that sensitivity of nucleic acid synthesis to Miracil D may be lost with a decrease in the differentiation of hepatic tissues.