Sequential Biochemical Alteration to Antifolate Resistance in L121O Leukaemia


ANTIFOLATE resistant, transplantable, murine tumours are most often characterized by a single change involving either the transport of drug1 or the level of dihydrofolate reductase2–5. This is understandable if one accepts the idea that multiple genetic events leading to an involvement of more than one physiological site rarely occur simultaneously. In two cases, where both physiological properties were altered6,7, the development of resistance probably occurred in a step-wise manner8. We have demonstrated this type of sequential alteration in resistance at both the physiological and cytogenetic level during repeated transplantation of a subline of L1210 leukaemia.

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SIROTNAK, F., KURITA, S., SARGENT, M. et al. Sequential Biochemical Alteration to Antifolate Resistance in L121O Leukaemia. Nature 216, 1236–1237 (1967).

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