An attempt at selective chemotherapy of hypoxic cells. Triethylenemelamine and irradiation of a C3H mouse mammary tumour
article
Hypoxic cells are resistant to radiation and, because they are predominantly non-cycling, to many antimetabolites. However, production of lactic acid by hypoxic cells in tumours probably leads to a rather low pH in the surrounding extracellular fluid; such cells might therefore be sensitive to cytotoxic drugs which are either selectively activated or selectively deposited under acidic conditions. We have used one such drug, the alkylating agent triethylenemelamine (TEM), with irradiation of a transplanted C3H mouse mammary tumour. Injection of TEM had no significant effect on the mean total dose of radiation (given either as a single dose or as 10 equal fractions) required to obtain local control of tumours in 50% of animals; however, the drug caused a significant prolongation in the time to tumour regrowth. Administration of glucose in the drinking water of the animals did not increase the effectiveness of tumour irradiation, or potentiate the action of TEM. Injection of TEM also had no influence on the time of appearance or severity of skin reactions after irradiation. The effect of TEM on proliferating and non-proliferating bone marrow stem cells was assayed by the spleen colony method: it was found that non-proliferating cells were more resistant to the drug. Thus, the resistance of hypoxic tumour cells to the lethal action of the drug might be due partly to their non-cycling state. © 1972.
Chemicals/CAS: glucose, 50-99-7, 84778-64-3; tretamine, 51-18-3; Glucose, 50-99-7; Triethylenemelamine, 51-18-3
Chemicals/CAS: glucose, 50-99-7, 84778-64-3; tretamine, 51-18-3; Glucose, 50-99-7; Triethylenemelamine, 51-18-3
Topics
glucosetretamineallotransplantationanimalanoxiacancer transplantationdrug effectexperimental neoplasmfemalehematopoietic stem cellmousemouse strainradiation doseAnimalAnoxiaFemaleGlucoseHematopoietic Stem CellsMammary Neoplasms, ExperimentalMiceMice, Inbred C3HNeoplasm TransplantationRadiotherapy DosageTransplantation, HomologousTriethylenemelamine
TNO Identifier
227352
ISSN
00142964
Source
European Journal of Cancer, 8(5), pp. 501-507.
Pages
501-507
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