Bulky DNA adducts_humans Protein adducts_animals Protein adducts_humans Chromosomal damage_CAs_animals Chromosomal damage_CAs_humans
+ (non-linear at high doses)
+ e.g. acrylamide, EMS, ethylene oxide (non-linear at high doses?), HPB, MeIQx, MMS, NNK, PhIP
+ e.g. acrylamide, aflatoxin, butadiene, ethylene oxide, propylene oxide, MeIQx
+ + < Inter-individual variation 4–8× (single study) Low (acrylamide, anhydrides); high (isocyanates) 0.4–7.9/108nt (20×, meta-analysis) Particularly of low molecular weight alkyl adducts; 4-ABP, rats, 500–3000 pg/g Hb; Dog, 118–240 pg/g Hb1
Particularly of low molecular weight alkyl adducts;
4-ABP, non-smokers, 28 pg/g Hb1
+ Smoking-related lung cancer; + Aflatoxin, liver cancer
+ Arylamine-Hb adducts, bladder cancer; + 4-ABP-Hb, smoking-relat-ed cancer (women)
+ High frequency associated with cancer risk, irrespective of exposure + DNA adducts in WBCs and lung cancer + PBLs used for studies on cancer risk Haemoglobin, serum albumin adducts ‘Long lifetime’ biomarker OECD validated OECD validated
8-oxodG 0.92/106dG; FPG 0.24/106; 0.24–0.75 lesions/106dG 86 Chromosomal damage_MN_animals Chromosomal damage_MN_humans DNA base oxidation_animals DNA base oxidation_humans + + + (threshold?) + Urinary 37%, 57% (2 subjects, 10 days); 48% (6 series, 8 months) Urinary 57% (6 series, 8 months). Residual variation in large no. of urinary studies, 20%. ESCODD, 8-oxodG 43%; FPG sites 49%
+ Medium and high MN frequencies associated with increased cancer risk
+ Case–control studies (reverse causality may be a problem); + Prospective study sug-gests higher risk of lung cancer in never smokers with higher urinary 8-oxodG
+ Dietary antioxidants/sup-plements reduce biomarker levels
+ PBLs used for studies on cancer risk; – Differences in buccal, nasal and blood cell MN levels after formaldehyde exposure – No correlation of 8-oxodG in leukocytes vs urinary metabo-lites in individuals HUMN validated HUMN validated Spurious oxidation during sample preparation has to be avoided Biomarker/exposure category Dose (exposure)–biomarker relationship Intra-individual variation Inter-individual variation
Background levels Biomarker–cancer relationship Surrogate/target tissue relationship Notes Modulation (intervention/ chemoprevention)
87 rs MeIQx ~1/109nt; PhIP ~1/109 Heterocyclic aromatic amines_animals Heterocyclic aromatic amines_humans
+ DNA, albumin, Hb adducts
+ Urinary HCAs, standard meat meals;
+ PhIP, MeIQx DNA adducts, feeding trials;
+ MeIQx-albumin, -Hb, oral
Large (urinary HCAs and metabolites)
+ DNA adducts found in tumour tissue; +/-- Feeding studies in cancer patients resulted in higher levels of PhIP but not MeIQx in tumour than normal tissue
+ Phenethylisothiocyanate & chlorophyllin decreased PhIP DNA adduct levels in liver, colon, prostate, blood in rats; + Dietary indole-3-carbinol inhibits PhIP- and IQ DNA adduct formation in mam-mary gland in mice; + Dietary ˆ-3 fatty acids inhibit PhIP DNA adduct formation in spleen in mice; -- Dietary genistein & lycopene increased PhIP DNA adduct levels in liver, colon, prostate, blood in rats + DNA adducts found in variety of tissues after dosing Sensitivity, specificity of methods need to be improved
88 N7meG, 2.5 DNA adducts/107nts; Urinary N7meG, 34 mg/g creatinine Polycyclic aromatic hydrocarbons_animals Polycyclic aromatic hydrocarbons_humans N-nitroso compounds_animals +
+ Dietary exposure increases urinary 1-OH pyrene glucuronide and DNA adducts in WBCs
+ O6mG;
+ N7meG; + HPB-Hb, HPB-DNA
+ Dose, DNA adduct and tumour formation show lin-ear correlation
+ PAH-DNA adducts in oesophageal biopsies of Chinese population with high dietary PAHs and high oesophageal cancer; + Prospective study sug-gests slightly higher risk of lung cancer in smokers with higher bulky DNA adduct levels in PBLs
+ O6mG, NDMA-induced
tumours;
+ HPB-DNA, NNK-induced lung cancer;
+ prospective study shows
+ AGT modulation in trans-genics of MNU-induced O6mG and cancer;
+ Lemon grass and bitter melon reduce AOM-induced
+ Correlations between B[a]P-DNA adducts in WBCs and lung, skin or sto-mach after dosing by different routes + O6mG WBCs vs. liver; + N7meG in WBCs vs. liver Urinary metabo-lites show prom-ise; high through-put DNA adduct methods required Biomarker/exposure category Dose (exposure)–biomarker relationship Intra-individual variation Inter-individual variation
Background levels Biomarker–cancer relationship Surrogate/target tissue relationship Notes Modulation (intervention/ chemoprevention)
89
rs
DNA and Hb adduct levels depend upon amounts of acrylamide in food consumed Background levels of Hb adducts found in unexposed non-smokers (dietary?) Acrylamide_animals Acrylamide_humans Alcohol_animals Alcohol_humans
red meat consumption
+ DNA adducts, MN, Hb adducts
+ Hb adducts and air/glove contamination; + Urinary metabolites and air levels; + Urinary metabolites, Hb adducts and smoking; + Hb adducts, high dietary intake in men
+ Hepatic N2
-ethyl-2'--deoxyguanosine increased by EtOH exposure; + Hepatic ÂdA, ÂdC increased by EtOH exposure
+ N2-ethyl-2'-deoxyguanosine
in liver, WBCs, urine increased by EtOH exposure
Hb adducts 5× in non-smokers; Similar or less in smokers/non-smo-kers for Hb adducts and urinary metabolites
– Epidemiological studies have shown no association of acrylamide and cancer (reflects lack of specificity of tumour induction?)
+ Liver N6
-ethenodeoxyade-nosine increased in patients with EtOH-related disease
Levels similar in vari-ous tissues required Dietary expo-sure difficult to assess; no DNA adduct data in humans Combination of biomarkers may be necesary
90
Aflatoxins_animals
Aflatoxins_humans
+ Albumin, DNA adducts, urinary AFB1-N-7-guanine
+ Albumin adducts, urinary AFB1-N-7-guanine
+ Urinary AFB1-N-7-gua-nine, liver cancer
+ Albumin adducts. hepa-tocarcinoma, Oltipraz + Albumin adducts, Oltipraz; + Urinary AFB1-N-7-gua-nine, Chlorophyllin + Correlation between AFB1-albu-min and liver DNA adducts Codon 249 mutation of p53 requires valida-tion as marker of risk Biomarker/exposure category Dose (exposure)–biomarker relationship Intra-individual variation Inter-individual variation
Background levels Biomarker–cancer relationship Surrogate/target tissue relationship Notes Modulation (intervention/ chemoprevention)
1See Sabbioni G, Jones CR. Biomonitoring of arylamines and nitroarenes. Biomarkers 2002;7:347–421 and references therein.
See text for references. +, relationship found; --, no relationship found; 4-ABP, 4-aminobiphenyl; 8-oxodG, 8-oxo-7,8-dihydro-2'-deoxyguanosine; ACF, aberrant crypt foci; Acro, acrolein; Cro, crotonaldehyde; AFB1, aflatoxin B1; AOM, azoxymethane;
B[a]P, benzo[a]pyrene; CA, chromosomal aberration; ÂdA, ethenodeoxyadenosine; ÂdC, 3,N4-ethenodeoxycytidine; EtOH, ethanol; Hb, haemoglobin; EMS, ethyl methane sulphonate; HCA, heterocyclic aromatic amine; HPB, hydroxypyridyloxobutyl;
IQ, 2-amino-3-methylimidazo[4,5-f]quinoline; M1G, pyrimido[1,2-a]purin-10(3H)-one; MDA, 4,4'-methylenediphenyldianiline; MeIQx, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline; MMS, methyl methane sulphonate; MN, micronucleus;
