Growth inhibitory and haematological effects of alkylating agents and attempts at their modification to give greater selectivity of anti-tumour action.

Abstract

SummaryAttempts to induce greater relative tumour specificity in cancer chemotherapeutic drugs may be aimed at (1) reducing toxicity towards host tissues or (2) increasing the susceptibility of the tumor.1. Pretreatment with certain thiol derivatives has some protective action against the host toxicity of X-irradiation and of certain alkylating agents. However, in many cases even better protection against the tumour-inhibitory action occurs so that the therapeutic index is unfavourably affected.2. Pretreatment with glucose which accentuates the pH difference between normal and tumour tissues can, in some cases, produce an increase in therapeutic index.3. The most encouraging aspect is to explore and take advantage of biochemical variations from the normal tissue pattern which are found in certain tumours, e.g. the successful treatment of the ADJ/PC5 mouse myeloma with «aniline mustard» is believed to be related to the very high glucuronidase activity of this tumour.