Oxygen free radical activity in experimental colonic carcinoma.

Abstract

Oxygen free radical activity has been implicated in carcinogenesis through DNA lysis. This study measured chemiluminescence and superoxide dismutase (SOD) inhibition as an index of oxygen free radical activity in azoxymethane-induced colonic carcinoma. After 3 weeks of acclimatization, ten Fisher 344 rats were injected with azoxymethane (7 mg kg-1 week-1) over 10 weeks. All animals were killed at 37 weeks and colonic mucosa (5-25 mg wet weight) was sampled from sites of histologically confirmed gross tumour and sites 3-5 cm distant from tumour as well as from ten paired normal controls. The samples were processed in buffered luminol and chemiluminescence was measured in a luminometer. Each sample was then placed in a solution of SOD for 3 min before a second chemiluminescence estimation. Mean(s.e.m.) chemiluminescence from control mucosal samples decreased from 8.1(1.0) to 3.9(1.1) mV per 100 mg tissue (P < 0.05) after incubation in SOD, suggesting that oxygen free radical activity was being measured. There was an increase to 20.2(0.9) mV per 100 mg in azoxymethane-treated colon remote from tumour and to 53.9(2.1) mV per 100 mg at tumour sites; both were reduced significantly after incubation with SOD to 6.7(0.7) and 11.0(0.8) mV per 100 mg respectively (P < 0.001). Chemiluminescence was significantly increased in azoxymethane-induced colonic carcinoma, both remote from and maximally at the tumour site, suggesting a field change in carcinogenesis associated with oxygen free radical activity.