van Maanen J M, Moonen E J, Maas L M, Kleinjans J C, van Schooten F J
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.
Carcinogenesis. 1994 Oct;15(10):2263-8. doi: 10.1093/carcin/15.10.2263.
With the aim of studying the effect of oral exposure to polycyclic aromatic hydrocarbons (PAH) on human DNA-adduct formation in mononuclear cells and excretion of 1-hydroxypyrene in urine, we examined the effect of consumption of charcoal-broiled hamburgers. Hamburgers were grilled and samples were homogenized, saponified, extracted with hexane and analysed for PAH content by HPLC. The mean levels of benzo[a]pyrene and pyrene in the grilled hamburgers were 8.6 and 26.5 micrograms/kg respectively. Twenty one healthy non-smoking individuals consumed two hamburgers (170 g) per day for 5 days. 32P-Postlabelling analysis was performed on DNA samples of mononuclear cells of the subjects. The excretion of 1-hydroxypyrene in urine was studied as a marker of endogenous exposure to PAH. In the DNA samples of eight of the 21 subjects, on day 3 of the consumption period a predominant adduct spot could be detected with similar chromatographic properties to a benzo[a]pyrenediolepoxide--deoxyguanosine standard, the levels varying between 3 and 103 adducts/10(10) nucleotides. Analysis of the urine samples revealed maximal 1-hydroxypyrene excretion on day 3 in all nine subjects who collected urine daily during the consumption week, with an average level of 5.2 nmol/24 h. In a subsequent study in which six volunteers consumed charcoal-broiled hamburgers with lower levels of benzo[a]pyrene and pyrene, no aromatic DNA adducts in mononuclear cells or increased 1-hydroxypyrene levels in urine were detected. In conclusion, oral intake of PAH may dose-dependent induce elevated levels of aromatic DNA adducts in mononuclear cells and of 1-hydroxypyrene in urine, indicating substantial bioactivation of PAH, in particular via this route.
为了研究经口暴露于多环芳烃(PAH)对人单核细胞中DNA加合物形成及尿中1-羟基芘排泄的影响,我们检测了食用炭烤汉堡包的影响。将汉堡包烤制后,样品匀浆、皂化、用己烷萃取,并用高效液相色谱法分析PAH含量。烤制汉堡包中苯并[a]芘和芘的平均含量分别为8.6微克/千克和26.5微克/千克。21名健康不吸烟个体每天食用两个汉堡包(170克),持续5天。对受试者单核细胞的DNA样品进行32P后标记分析。研究尿中1-羟基芘的排泄作为内源性PAH暴露的标志物。在21名受试者中的8名的DNA样品中,在食用期第3天可检测到一个主要加合物斑点,其色谱性质与苯并[a]芘二环氧物-脱氧鸟苷标准品相似,加合物水平在3至103个加合物/10(10)个核苷酸之间变化。对尿样的分析显示,在食用周期间每天收集尿液的所有9名受试者中,第3天1-羟基芘排泄量最高,平均水平为5.2纳摩尔/24小时。在随后的一项研究中,6名志愿者食用了苯并[a]芘和芘含量较低的炭烤汉堡包,未检测到单核细胞中有芳香族DNA加合物或尿中1-羟基芘水平升高。总之,经口摄入PAH可能会剂量依赖性地导致单核细胞中芳香族DNA加合物水平升高以及尿中1-羟基芘水平升高,这表明PAH有显著的生物活化作用,尤其是通过这种途径。