FORMATION OF AROMATIC DNA-ADDUCTS IN WHITE BLOOD-CELLS IN RELATION TOURINARY-EXCRETION OF 1-HYDROXYPYRENE DURING CONSUMPTION OF GRILLED MEAT

With the aim of studying the effect of oral exposure to polycyclic aro matic hydrocarbons (PAH) on human DNA - adduct formation in mononuclea r cells and excretion of 1-hydroxypyrene in urine, we examined the eff ect of consumption of charcoal-broiled hamburgers. Hamburgers were gri lled and samples were homogenized, saponified, extracted with hexane a nd 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 mu g/kg respec tively. Twenty one healthy non-smoking individuals consumed two hambur gers (170 g) per day for 5 days. P-32-Postlabelling analysis was perfo rmed on DNA samples of mononuclear cells of the subjects. The excretio n of 1-hydroxypyrene in urine was studied as a marker of endogenous ex posure 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 detecte d with similar chromatographic properties to a benzo[a]pyrenediolepoxi de - deoxyguanosine standard, the levels varying between 3 and 103 add ucts/10(10) nucleotides. Analysis of the urine samples revealed maxima l 1-hydroxypyrene excretion on day 3 in all nine subjects who collecte d 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 ch arcoal-broiled hamburgers with lower levels of benzo[a]pyrene and pyre ne, no aromatic DNA adducts in mononuclear cells or increased 1-hydrox ypyrene levels in urine were detected. In conclusion, oral intake of P AH may dose-dependently induce elevated levels of aromatic DNA adducts in mononuclear cells and of 1-hydroxypyrene in urine, indicating subs tantial bioactivation of PAH, in particular via this route.