Hydroxyl radical generation by respirable industrial fibres

Asbestos fibres are known to cause lung cancer and mesothelioma but less is known of the carcinogenic potential of man-made fibres such as glass fibre. Recent animal experimental studies have suggested that previous data indicating that the 3 properties that rendered an asbestos fibre carcinogenic:- long, thin and durable in the lung, may not be adequate to explain the carcinogenicity of non-asbestos fibres. The additional actor could be the free radical activity of the fibres, supported by evidence of oxidative stress and depletion of antioxidant defences in fibre-exposed lungs. In order to address the hypothesis that the free radical activity of fibres is a factor in carcinogenicity we utilised a panel of 6 different respirable industrial fibres. These 6 samples were divided into 3 pathogenic fibres - amosite asbestos, silicon carbide and a kaolin-based refractory ceramic fibre (RCF 1), and 3 non-pathogenic fibres- man-made vitreous fibre (MMVF) 11, Code 100/475 glass fibre and a heat-treated version of RCF1, designated RCF4. All experiments were carried out with equal fibre numbers. Two assays of free radical activity were used:- 1) a plasmid assay of DNA scission which showed only amosite asbestos to have free radical activity (55% depletion of supercoiled DNA) ; 2) a salicylate assay of hydroxyl activity which revealed both amosite asbestos and RCF1 to release hydroxyl radicals (data is mean (SEM) nmol hydroxyl radicals in 3 separate experiments):- amosite asbestos 0.45 (0.05); RCF1 1.0 (0.05). None of the non-pathogenic fibres demonstrated free radical activity in either of the assays. In the presence of the hydroxyl radical scavenger mannitol there was a significant lowering of hydroxyl radical production by both LFA and RCF1 (data as above):- amosite asbestos 1.25 (0.39); amosite asbestos + mannitol 0.72 (0.26). The reason that only the salicylate assay demonstrated free radical activity with RCF1 was likely due to increased release of iron from RCF1 under the more acid conditions of the salicylate assay. The ability of a fibre to release hydroxyl radicals may be an important factor in its carcinogenicity.