Formation of aromatic DNA adducts in white blood cells in relation to urinary excretion of 1-hydroxypyrene during consumption of grilled meat.
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.
van Maanen
J M
JM
Department of Health Risk Analysis and Toxicology, University of Limburg, Maastricht, The Netherlands.
Moonen
E J
EJ
Maas
L M
LM
Kleinjans
J C
JC
van Schooten
F J
FJ
D000328:Adult; D000818:Animals; D002417:Cattle; D018736:DNA Adducts / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006358:Hot Temperature; D006801:Humans; D007962:Leukocytes / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008460:Meat; D008875:Middle Aged; D011083:Polycyclic Compounds / Q000097:blood*; D011721:Pyrenes / Q000493:pharmacokinetics*
D018736:DNA Adducts; D011083:Polycyclic Compounds; D011721:Pyrenes; C033146:1-hydroxypyrene