Cytological effects of sulfur and selenium purine analogues on two transplantable hepatomas and on normal renewing cells in mice.

The effects of 50% lethal doses of three purine analogues, 6-methylmercaptopurine riboside ( MMPR ), 6-thioguanosine (TGR), and 6- selenoguanosine ( SeGR ), on mitotic activity in a slow-growing ( SS1H ) and a fast-growing ( BH3 ) transplantable hepatocellular adenoma in C3H/ StW and BUB mice, respectively, were analyzed statistically. No significant difference in response was found between the two benign hepatomas. MMPR alone effectively reduced mitotic activity in the tumors and did so as efficiently on the first day of treatment as on subsequent days of daily i.p. administrations for up to 10 days. TGR alone and SeGR alone were ineffective in reducing the mitotic index significantly below that of controls. When either TGR or SeGR was injected simultaneously with MMPR , the effect on tumor mitosis resembled that of MMPR alone. The reactions of normal cells of the hosts to these agents were analyzed quantitatively in duodenal epithelium with respect to mitotic activity and to the number of cells present in the crypts. Differences between the two strains of mice were small and, for the most part, not significant. MMPR produced a slight but not significant reduction in duodenal mitotic activity and cell number. TGR alone induced significant decreases in both after 3 and 5 days of treatment. SeGR alone had no effect on the duodena . The effects of a combination of SeGR with MMPR on the duodena differed only slightly from MMPR or SeGR alone, but TGR plus MMPR produced greater inhibition of mitosis than did either administered alone. Our results suggest that MMPR may be a promising chemotherapeutic agent against some types of solid hepatocellular tumors in vivo because it can inhibit mitosis in these tumors effectively, rapidly, and continuously, while its inhibitory effect on normal replicating cells of the host intestine occurs more slowly and only with long-sustained treatment.