Evidence of anti-benzo[a]pyrene diolepoxide-DNA adduct formation in human colon mucosa.
As risk factors for colorectal cancer include consumption of foods potentially contaminated with polycyclic aromatic hydrocarbons (PAHs), the level of (+)-r-7,t-8-dihydroxy-t-9,10-oxy-7,8,9,10-tetrahydrobenzo[a]pyrene [(+)-anti-BPDE] bound to DNA of human colon mucosa samples was quantified by a sensitive and specific HPLC/fluorescence method (Alexandrov et al., Cancer Res. 51, 6248-6253, 1992). (+)-anti-BPDE-DNA adducts were detected in four out of seven colon mucosa samples but not in any of 11 human pancreas samples from smokers and non-smokers. Adduct levels in human colon varied between 0.2 and 1.0 (+)-anti-BPDE-DNA adducts/10(8) nucleotides. Our results provide evidence that: (i) the DNA in human colon cells can be damaged by benzo[a]pyrene, possibly derived from diet and/or tobacco smoke; (ii) DNA adduct formation in human colon epithelium proceeds via the diol epoxide pathway; (iii) benzo[a]pyrene and other PAHs could play a role in the etiology of human colorectal cancer.
Alexandrov
K
K
Deutsches Krebsforchungszentrum, Division of Toxicology and Cancer Risk Factors, Heidelberg, Germany.
Rojas
M
M
Kadlubar
F F
FF
Lang
N P
NP
Bartsch
H
H
D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D003106:Colon; D015179:Colorectal Neoplasms / Q000209:etiology; D018736:DNA Adducts / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D009928:Organ Specificity; D010179:Pancreas / Q000378:metabolism; D012907:Smoking; D013050:Spectrometry, Fluorescence; D013237:Stereoisomerism
D018736:DNA Adducts; C043931:benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide-DNA; D015123:7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide