Hemoglobin adducts of aromatic amines: associations with smoking status and type of tobacco.

Bryant, Matthew; Víneis, Paolo; Skipper, Paul L.; Tannenbaum, Steven R.

doi:10.1073/pnas.85.24.9788

Cited by 169 publications

(124 citation statements)

References 16 publications

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“…A convex dose-response curve was also observed for the correlation of the concentration of 4-ABP-hemoglobin adducts with markers of recent smoking (number of cigarettes, urinary cotinine and nicotine) (6,11). Such a relationship would be expected a priori if the population included two subgroups -one that metabolizes the relevant chemical rapidly and the other, slowly.…”

Section: Doseresponse Relationshipsmentioning

confidence: 78%

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Víneis¹,

Ronco²

1992

Environ Health Perspect

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Epidemiological studies indicate that subjects of the genetically based slow acetylator phenotype may be at higher risk for bladder cancer than fast acetylators, particularly when they are exposed to carcinogenic arylamines: N-acetylation is a detoxification step in the metabolism of some arylamines. We describe two collaborative studies on tobacco smoking, in which markers of internal dose (arylamine-hemoglobin adducts) and markers of genetically based metabolic polymorphism have been coupled. In the first investigation, we found that hemoglobin adducts formed by mononuclear arylamines have high reciprocal correlation coefficients, as do adducts from binuclear arylamines. This tendency of adducts with structurally similar arylamines to correlate reciprocally explains a large proportion ofthe residual variance seen after controlling for smoking habits (number and type of cigarettes). In the second study, the concentration of 4-aminobiphenyl-hemoglobin adducts varied according to three independent determinants: number of cigarettes, type of tobacco (air or flue cured), and acetylator phenotype (slow and fast). The dose-response relationship between the amount of tobacco smoked and level of 4-aminobiphenyl-hemoglobin adducts in the slow acetylators (with an immediate steep increase of the adducts) was different from that in the fast acetylators (with a more regular increase). These findings from "molecular epidemiology" may contribute to an understanding of the role of metabolic polymorphism in human carcinogenesis.

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Section: Doseresponse Relationshipsmentioning

confidence: 78%

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Víneis¹,

Ronco²

1992

Environ Health Perspect

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“…Levels of 4-aminobiphenyl were also not significantly different between smokers (78.6 Ϯ 85.2 ng/24 hr) and nonsmokers (68.1 Ϯ 91.5 ng/24 hr) [Grimmer et al, 2000]. In contrast, 4-aminobiphenyl-hemoglobin adducts are generally higher in smokers than in nonsmokers [Bryant et al, 1988]. Levels of these adducts are also modified by variants in carcinogen-metabolizing enzymes.…”

Section: Uptake and Metabolic Activation Of Breast Carcinogens In Smomentioning

confidence: 86%

Tobacco smoke carcinogens and breast cancer

Hecht

2002

Environ and Mol Mutagen

186

143

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Cigarette smoking is an established cause of a variety of cancer types, but its role in breast cancer etiology is not clear. In this report, the potential role of cigarette smoke carcinogens as causes of human breast cancer is evaluated. Of over 60 known carcinogens in tobacco smoke, several are known to induce mammary tumors in laboratory animals: [4,5-b]pyridine (PhIP), 1,3-butadiene, isoprene, nitromethane, ethylene oxide, and benzene. Studies in humans demonstrate that tobacco constituents can reach breast tissue. The uptake and metabolic activation of mammary carcinogens such as polycyclic aromatic hydrocarbons (PAHs) and 4-aminobiphenyl are frequently higher in smokers than in nonsmokers. Although it is likely that specific mammary carcinogens in tobacco smoke can reach breast tissue, evidence is lacking at the present time. Some PAHs present in cigarette smoke can be metabolized to sterically hindered diol epoxides, which are potent mammary carcinogens. Thus, compounds such as benzo[c]phenanthrene (B[c]P), not classically considered to be a strong carcinogen in rodents, could nevertheless be metabolized in humans to diol epoxides carcinogenic to the breast. Collectively, the link between smoking and breast cancer is plausible but has been difficult to establish, probably because of the low carcinogen dose. Environ. Mol.

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“…Subjects and materials included in the present analysis are the same described in the previous report, which also describes laboratory procedures (Bryant et al, 1988).…”

Section: Methodsmentioning

confidence: 99%

Haemoglobin adducts formed by aromatic amines in smokers: sources of inter-individual variability

Ronco¹,

Víneis²,

Bryant³

et al. 1990

Br J Cancer

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Summary In a previous study we found that aromatic amines, particularly 4-aminobiphenyl, formed haemoglobin adducts at higher concentrations in the blood of smokers compared to non-smokers. We re-analyse here data on haemoglobin adducts of 14 aromatic amines in order to ascertain if the inter-individual variability left unexplained by tobacco smoking could be attributed to differences in individual metabolic patterns. For this purpose we computed residuals from analysis of variance in order to adjust for individual smoking habits (type and amount of tobacco). Residuals were correlated within two clearly distinct groups: one formed by binuclear compounds (4-aminobiphenyl, 3-aminobiphenyl and 2-naphthylamine) and the other formed by all other (i.e. mononuclear) compounds. Within each group, highly statistically significant correlation coefficients were found, whereas compounds belonging to one group were not correlated to compounds in the other group. These results can be interpreted as a suggestion that two different metabolic pathways exist, one for binuclear and one for mononuclear arylamines, and that inter-individual differences in such pathways can explain part of inter-individual variability in adduct levels. This interpretation is consistent with recent animal experiments suggesting that there are different enzyme systems for the two classes of compounds.In a previously published paper, Bryant et al. (1988) reported that the quantity of haemoglobin adducts of 3-aminobiphenyl (3-ABP) and 4-aminobiphenyl (4-ABP) was related to the number of cigarettes smoked and, for 4-ABP, to the kind of tobacco (air-or flue-cured). However, the amount and type of tobacco smoked left unexplained a considerable proportion of inter-individual variability of haemoglobin adducts of the 14 investigated arylamines, including 3-ABP, 4-ABP and 2-naphthylaine (2-NA).4-ABP and 2-NA are well known bladder carcinogens, in both humans and experimental animals (IARC, 1987). Of the 14 investigated arylamines, three were binuclear: 3-ABP and 4-ABP are formed by two benzene rings and 2-NA is a naphthalene derivative; all the others have a single aromatic ring.Here we re-analyse the same data set in order to ascertain whether the unexplained residual variability might be related to differences in individual metabolic patterns. If individual metabolic differences were responsible for part of the so far unexplained inter-individual variability in haemoglobin adducts and if chemically similar substances had, at least in part, common metabolic pathways, then one would expect the concentrations of adducts of similar amines to be correlated in the same individual, after allowing for amount and type of tobacco smoked. In other words, if the hypothesis is correct, after allowing for smoking habits, subjects showing high levels of 4-ABP adducts should also have high levels of 3-ABP adducts and subjects showing low levels of 4-ABP should also have low levels of 3-ABP. Materials and methodsSubjects and materials included in the present analysis are th...

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Hemoglobin adducts of aromatic amines: associations with smoking status and type of tobacco.

Cited by 169 publications

References 16 publications

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Interindividual variation in carcinogen metabolism and bladder cancer risk.

Tobacco smoke carcinogens and breast cancer

Haemoglobin adducts formed by aromatic amines in smokers: sources of inter-individual variability

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