3-nitrobenzanthrone, a potential human cancer hazard in diesel exhaust and urban air pollution: a review of the evidence

Epidemiological studies have shown that exposure to diesel exhaust and urban air pollution is associated with an increased risk of lung cancer. 3-Nitrobenzanthrone [3-nitro-7H-benz[de]anthracen-7-one (3-NBA)] is an extremely potent mutagen and suspected human carcinogen identified in diesel exhaust and ambient air particulate matter. The main metabolite of 3-NBA, 3-aminobenzanthrone (3-ABA), was found in the urine of salt mine workers occupationally exposed to diesel emissions, indicating that human exposure to 3-NBA due to diesel emissions can be significant and is detectable. There is clear evidence that 3-NBA is a genotoxic mutagen forming DNA adducts after metabolic activation through simple reduction of the nitro group. Several human enzymes have been shown to activate 3-NBA and its metabolites in vitro and in cells to form electrophilic arylnitrenium and rearranged carbenium ions, leading to the formation of purine adducts at the C8 and N-2 position of guanine and at the C8 and N-6 position of adenine. The predominant DNA adducts in vivo, 2-(2'-deoxyguanosin-N-2-yl)-3-aminobenzanthrone and N-(2'-deoxyguanosin-8-yl)-3-aminobenzanthrone are also the most persistent adducts in target tissue in rodents, and are most probably responsible for the induction of GC -> TA transversion mutations observed in vivo. It is concluded that these adducts not only represent premutagenic lesions in DNA but are of primary importance for the initiation of the carcinogenic process and subsequent tumour formation in target tissue. Indeed, 3-NBA is carcinogenic in rats after intratracheal instillation, inducing mainly squamous cell carcinoma in lung. The intention of this article is to provide a critical review on the potential genotoxic effects of 3-NBA on human health. However, in general, there is a need for more mechanistic studies that relate 3-NBA to all processes that are considered to orchestrate tumour development and of studies on the ability of particles to promote 3-NBA genotoxicity. Because of its widespread environmental presence, 3-NBA may represent not only an occupational health hazard but also a hazard for larger sections of the general population. For an accurate risk assessment more epidemiological studies on 3-NBA-exposed individuals and a broader monitoring of environmental levels of 3-NBA are required.