Clonfero E, Granella M, Marchioro M, Barra E L, Nardini B, Ferri G, Foà V
Institute of Occupational Health, University of Padova, Italy.
Carcinogenesis. 1995 Mar;16(3):547-54. doi: 10.1093/carcin/16.3.547.
The influence of occupational exposure to polycyclic aromatic hydrocarbons (PAHs) on urinary mutagenic activity was assessed in 75 coke oven workers, using a highly sensitive bacterial mutagen technique (extraction with C18 resin and liquid micro-preincubation test on strain TA98 of Salmonella typhimurium in the presence of metabolizing and deconjugating enzymes). Exposure to PAHs was assessed according to the urinary excretion of 1-pyrenol; the main confounding factors were checked by the number of cigarettes smoked per day and the levels of nicotine and its metabolites in urine, or by ascertaining whether recommended dietary restrictions had been followed. Of the 20 urine samples which turned out to be positive (producing at least double the number of spontaneous revertants), 19 (95%) belonged to smokers. Only one non-smoker had obvious urinary mutagenic activity, and was highly exposed occupationally to PAHs (urinary 1-pyrenol of 3.930 mumol/mol of creatinine). Of the five urine samples from subjects who had not followed the recommended diet, two (40%) were clearly mutagenic. Multiple regression analysis (n = 67) showed that the presence of samples positive for urinary mutagenic activity depended only on smoking habits, if this confounding factor was assessed according to the number of cigarettes smoked per day, while the significant influence of exposure to PAH could be shown when the confounding factor was objectively estimated according to the urinary levels of nicotine and its metabolites. Assessment of the mutagenic potency of urinary extracts (net revertants/mmol creatinine) confirmed the strong influence of smoking habits on urinary mutagenic activity (all smokers 2156 +/- 2691 versus non-smokers 939 +/- 947 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). In smokers highly exposed to PAHs, greater excretion of mutagens with respect to low-exposure smokers was revealed (3548 +/- 4009 versus 1552 +/- 1227 net revertants/mmol creatinine; Mann-Whitney test: P < 0.01). Multiple regression analysis showed that the mutagenic potency of urinary extracts of coke oven workers depended on exposure to PAHs, tobacco smoking habits, and consumption of fried, grilled or barbecued meat. Increased urinary mutagenic activity strengthens epidemiological evidence of the increased risk of renal and urinary tract tumours in these workers. The presence of mutagenic metabolites in urine as a result of occupational exposure to PAH may be demonstrated only by using highly sensitive techniques for assessing urinary mutagenic activity in studies which include careful checking of the main confounding factors.
采用高灵敏度细菌诱变技术(用C18树脂萃取,并在代谢和去共轭酶存在的情况下对鼠伤寒沙门氏菌TA98菌株进行液体微量预培养试验),对75名炼焦炉工人职业接触多环芳烃(PAHs)对尿诱变活性的影响进行了评估。根据尿中1-芘醇的排泄量评估PAHs暴露情况;主要混杂因素通过每日吸烟量以及尿中尼古丁及其代谢产物水平进行核查,或者通过确定是否遵循了推荐的饮食限制来核查。在检测出呈阳性的20份尿样(回复突变体数量至少为自发回复突变体数量的两倍)中,有19份(95%)属于吸烟者。只有一名不吸烟者有明显的尿诱变活性,且其职业性PAHs暴露程度很高(尿中1-芘醇为3.930 μmol/mol肌酐)。在未遵循推荐饮食的受试者的5份尿样中,有2份(40%)明显具有诱变性。多元回归分析(n = 67)表明,如果根据每日吸烟量评估这一混杂因素,尿诱变活性呈阳性的样本的存在仅取决于吸烟习惯,而当根据尿中尼古丁及其代谢产物水平客观评估混杂因素时,可显示出PAH暴露的显著影响。尿提取物诱变效力(净回复突变体/mmol肌酐)的评估证实了吸烟习惯对尿诱变活性有很大影响(所有吸烟者为2156±2691净回复突变体/mmol肌酐,而不吸烟者为939±947净回复突变体/mmol肌酐;Mann-Whitney检验:P < 0.01)。在PAHs高暴露的吸烟者中,相对于低暴露吸烟者,诱变剂排泄量更高(3548±4009净回复突变体/mmol肌酐对1552±1227净回复突变体/mmol肌酐;Mann-Whitney检验:P < 0.01)。多元回归分析表明,炼焦炉工人尿提取物的诱变效力取决于PAHs暴露、吸烟习惯以及油炸、烧烤或烤肉的摄入量。尿诱变活性增加强化了这些工人患肾和尿路肿瘤风险增加的流行病学证据。只有在研究中使用高灵敏度技术评估尿诱变活性,并仔细核查主要混杂因素时,才能证明职业性PAH暴露导致尿中存在诱变代谢产物。