Apparent synergy between chrysotile asbestos and N-nitrosoheptamethyleneimine in the induction of pulmonary tumours in rats

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Abstract
Environmental carcinogenesis in man is widely accepted to be a multifactorial process, and in the causation of lung cancers it is suspected that low levels of systemic carcinogens may act synergistically with inhaled particulates so that some exposed individuals are at increased risk. In the present study the carcinogenic effects of low levels of industrially/environmentally significant particulate materials (chrysotile asbestos and metallic cadmium) and a putative systemiccarcinogen, N -nitrosoheptamethyleneimine (NHMI), were investigated in the laboratory rat, using this as amodel of potential human exposure. The overall lung tumour incidence rate in the groups of animals receiving chrysotile and NHIMI together (8/50) or chrysotile, cadmium and NHMI together (6/44) was substantially higher than in thegroups receiving chrysotile alone (1/86) or chrysotile and cadmium (1/94) or NIIMI alone (2/48). The results demonstrated apparent synergy between chrysotile and NHMI in the induction of lung tumours. Incidence of pulmonaryhyperplastic lesions paralleled the trend in tumour incidence. Cadmium had little or no influence on the incidence of either lung tumours or hyperplastic lesions. This study helps to evaluate further the role of asbestos in the causation of lung cancer. It is suggested that people who are or have been exposed to chrysotile asbestos may show a significantly elevated risk of lung cancer if concomitantly or subsequently exposed to tumour initiating agents.