Routes of conjugation in normal and cancerous tissue from human lung

Abstract

The selective toxicity of drugs leading to major advances in antibacterial chemotherapy has often resulted from the identification and exploitation of major biochemical differences between bacterial and mammalian species¹. Similar progress has not been made in cancer chemotherapy, partly due to a lack of suitable biochemical differences between normal and cancerous tissue other than in DNA synthesis, but also because of many other problems such as those of metastases and resistance, and the presence in tumours of cells at different states of the cell cycle. Here we report a major biochemical difference in the routes of conjugation between normal lung and tumour tissue from patients with lung cancer. Conjugation with glucuronic acid and sulphate constitute two of the most important pathways of metabolism of drugs, other foreign compounds and hormonal steroids^2,3. Using 1-naphthol as a model phenolic substrate, normal peripheral lung tissue formed almost exclusively the sulphate ester conjugate, 1-naphthyl sulphate, whereas tumour tissue from squamous carcinomas from the same patients formed predominantly the glucuronic acid conjugate, 1-naphthyl glucuronide. Such major biochemical differences may be exploitable in the design of selectively toxic cancer chemotherapeutic agents.