Antitumor activity of mono- and dimetallic transition metal carborane complexes of Ta, Fe, Co, Mo, or W.

Complexes containing Ta, Fe, Co, Mo, or W metal centers that are bound to C2B4 or C2B3 small carborane ligands proved to be potent cytotoxic agents in murine and human tissue cultured cells, being more effective in suspended leukemia and lymphomas but surprisingly also effective against the growth of selected solid tumors. These complexes inhibited nucleic acid metabolism, specifically DNA and purine de novo syntheses. Key enzyme activities in nucleic acid metabolism which were inhibited by the complexes were P388 DNA polymerase a, ribonucleotide reductase, dihyrofolate reductase, PRRP-amidotransferase and IMP dehydrogenase. The complexes afforded a moderate amount of DNA-fragmentation in P388 lymhocytic leukemia cells and were moderate inhibitors of human DNA topoisomerase II activity; however, the DNA molecule itself was not a target of the complexes in that there was no evidence that the complexes caused intercalation between base pairs, caused cross-linking of the strands of DNA or alkylated the bases of DNA.

Cytotoxicity of copper and cobalt complexes of furfural semicarbazone and thiosemicarbazone derivatives in murine and human tumor cell lines.

The 2-furfural semicarbazone and thiosemicarbazone copper and cobalt complexes demonstrated potent cytotoxicity against the growth of suspended leukemias and lymphomas as well as human lung MB9812, colon SW480, ovary 1-A9 and HeLa-S3 uterine carcinoma. In L1210 lymphoid leukemia cell the complexes inhibited preferentially DNA synthesis over 60 min at 25 to 100 microM. The copper and cobalt complexes functioned by multiple mechanisms to suppress synthetic steps in nucleic acid metabolism to reduce deoxynucleotide pools for incorporation into DNA. At high concentrations the complexes suppressed human DNA topoisomerase II activity with DNA nicks and DNA fragmentation but they did not alkylate the bases of DNA, cause intercalation between base pairs or cause cross-linking of DNA strands.

Dose equivalent commitments from fallout radionuclides in the open waters of the Great Lakes. 1973-1981.

The levels of (144)Ce, (137)Cs, (125)Sb, and (90)Sr in the open waters of the Great Lakes were measured over the period 1973-81. The levels were found to be very low. (144)Ce was detected only up to 1975 after which it dropped below the detection limit. The data indicate that the concentrations of the remaining three radionuclides have decreased with time. (90)Sr and (137)Cs provide essentially all of the radiological dose from drinking Great Lakes water. The dose equivalant commitments have been calculated from these measurements and found to be well within the Great Lakes Water Quality Agreement's water quality objective for radioactivity.