The radioprotector zinc aspartate did not inhibit the radiotherapeutic effect of gamma rays on human tumours grown as xenografts in immunosuppressed mice, while aminothiol radioprotectors afforded a slight inhibition. On the other hand, zinc aspartate significantly reduced the fall in the haematocrit and numbers of thrombocytes, erythrocytes and leucocytes caused by irradiation, indicating a sparing effect on bone marrow precursors of peripheral blood cells. This differential protection of neoplastic and normal cells may be of considerable benefit in clinical cancer radiotherapy, provided that zinc aspartate is better tolerated and has a more favourable therapeutic index in humans than aminothiol radioprotectors.

The organic zinc salts zinc aspartate, zinc histidine, zinc orotate and zinc acetate reduced the fall of the haematocrit, thrombocytes, erythrocytes and leucocytes in irradiated mice. In general, zinc aspartate was more effective than the other organic zinc salts. Protection of the haematocrit and thrombocytes by small doses of the aminothiol radioprotector WR 2721 was markedly improved by the concomitant administration of small doses of zinc aspartate. Zinc aspartate was the only one of the four tested organic zinc salts that did not inhibit in any instance the regression induced by radiotherapy of human tumours grown as xenografts in immunosuppressed mice. This also applied to the combination of zinc aspartate with WR 2721. In an experiment performed to determine the toxicity of the combined regimen, a dose of zinc aspartate which afforded synergistic haematological protection did not enhance the toxicity of WR 2721. The synergism of zinc aspartate with WR 2721 and the differential radioprotection of the combined protocol may make it possible in clinical cancer radiotherapy to obtain selective radioprotection at a lower toxicity giving an improved therapeutic ratio compared with WR 2721 alone.

Survival of mice after lethal doses of lyophilizate from Amanita phalloides ('death cap') was markedly increased by pretreatment with single doses of kutkin, a mixture of iridoid glycosides picroside I and kutkoside isolated from the roots of Picrorhiza kurroa. The protective effect of kutkin was comparable to that of silibinin. The curative efficacy of kutkin appeared to be slightly superior.

A human tumor xenograft model using pharmacologically immunosuppressed mice was assessed for its suitability to test preclinically the sensitivity of colorectal carcinomas, bone sarcomas and melanomas against anticancer agents. Besides ionizing radiation, 14 cytotoxic drugs including 5-fluorouracil (5-FU), dimethylmyleran (DMM), cytosine arabinoside, cyclophosphamide, melphalan, BCNU, mitomycin C, adriamycin, bleomycin, etoposide, vinblastine, cisplatin, procarbazine and DTIC were assayed. Ionizing radiation, 5-FU and DMM were also applied at lethal doses followed by bone-marrow rescue heavy therapy. Four colon carcinomas responded poorly to most of the agents but one tumor displayed marked sensitivity to BCNU. Lethal doses of radiation, 5-FU and DMM could also show considerable activity. High sensitivity was shown by a Ewing sarcoma to DMM and cyclophosphamide and by an osteosarcoma to the latter drug. No strong effects were seen against melanomas. Lethal doses of DMM induced the best regression of one colon carcinoma. In general, the superiority of heavy therapy for solid human tumors compared to maximally tolerated doses was demonstrated. Individual carcinomas of the same type displayed different drug sensitivity.

No abstract