Interindividual Variation in Binding of Benzo[
            <i>a</i>
            ]pyrene to DNA in Cultured Human Bronchi

Harris, Curtis C.; Autrup, Herman; Connor, Robert D.; Barrett, Lucy A.; McDowell, Elizabeth M.; Trump, Benjamin F.

doi:10.1126/science.982061

Cited by 131 publications

(43 citation statements)

References 8 publications

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“…DNA was purified from tracheal cells by phenol extraction, solvent extraction of unreacted BP, enzymatic removal of protein and RNA, followed by banding at equilibrium in centrifugally generated CsCl gradients. These techniques were applied to the isolation of DNA from human bronchial tissues (15,20,(25)(26)(27). Though the quantities of DNA isolated are often on the order of micrograms, this has proven sufficient to allow BP-DNA adduct analyses in a variety of species including hamsters, rats, mice, bovines and humans (28).…”

Section: Methods For Biochemical Study Of Tracheobronchial Epitheliummentioning

confidence: 99%

“…In a study of the levels of binding of BP and DMBA assessed in 28 specimens of human bronchus, the mean level for DMBA-DNA binding was 118 pmole/10 mg DNA and that of BP-DNA binding was 38 pmole/10 mg DNA, indicating that DMBA was bound to a significantly greater extent. The levels of binding of BP to bronchial DNA were studied more intensively in 37 specimens from patients with or without lung cancer (25). The specimens were obtained either after immediate autopsy or during surgery to ensure the viability of the tissues.…”

Section: Carcinogen Metabolism and Binding In Human Respiratory Tissuesmentioning

confidence: 99%

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Biochemical Studies of the Tracheobronchial Epithelium

Mass¹,

Kaufman²

1984

Environmental Health Perspectives

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Tracheobronchial epithelium has been a focus of intense investigation in the field of chemical carcinogenesis. We have reviewed some biochemical investigations that have evolved through linkage with carcinogenesis research. These areas of investigation have included kinetics of carcinogen metabolism, identification of carcinogen metabolites, levels of carcinogen binding to DNA, and analysis of carcinogen-DNA adducts. Such studies appear to have provided a reasonable explanation for the susceptibilities of the respiratory tracts of rats and hamsters to carcinogenesis by benzo(a)pyrene. Coinciding with the attempts to understand the initiation of carcinogenesis in the respiratory tract has also been a major thrust aimed at effecting its prevention both in humans and in animal models for human bronchogenic carcinoma. These studies have concerned the effects of derivatives of vitamin A (retinoids) and their influence on normal cell biology and biochemistry of this tissue. Recent investigations have included the effects of retinoid deficiency on the synthesis of RNA and the identification of RNA species associated with this biological state, and also have included the effects of retinoids on the synthesis of mucus-related glycoproteins.Tracheal organ cultures from retinoid-deficient hamsters have been used successfully to indicate the potency of synthetic retinoids by monitoring the reversal of squamous metaplasia. Techniques applied to this tissue have also served to elucidate features of the metabolism of retinoic acid using high pressure liquid chromatography. In brief, formidable strides have been made in biochemistry specific to this important target tissue, despite the inability to acquire tracheobronchial epithelium in large quantities.

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Section: Methods For Biochemical Study Of Tracheobronchial Epitheliummentioning

confidence: 99%

Section: Carcinogen Metabolism and Binding In Human Respiratory Tissuesmentioning

confidence: 99%

Biochemical Studies of the Tracheobronchial Epithelium

Mass¹,

Kaufman²

1984

Environmental Health Perspectives

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“…Also, McLemore et al (1978b) reported no difference between lung cancer cases and controls in AHH activity in pulmonary alveolar macrophages obtained by lavage. In three uncontrolled studies (Harris et al, 1976;Cohen et al, 1979;Sabadie et al, 1981), AHH activity in cultured bronchus or peripheral lung tissue of patients with lung cancer showed, like the controlled studies, wide unimodal distribution (20-, 44-and Karki et al, 1987).…”

Section: Phase II Conjugationmentioning

confidence: 99%

Genetic predisposition to lung cancer

1983

European Journal of Cancer and Clinical Oncology

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In Britain, the life-time risk of lung cancer in men who smoke 20 or more cigarettes per day is about 15%. That most smokers never develop lung cancer has promoted interest in the role of host factors. While chance, other environmental factors and the competing effect of other diseases, some of which are also smoking related, are all likely to affect individual lung cancer risk, genetic factors may also be important. This review examines the evidence for genetic predisposition to smoking related lung cancer.The review concentrates on the numerous metabolic studies that have sought differences between individuals in the genetic control of biochemical pathways that could be involved in the metabolism of carcinogens in tobacco smoke. Insights gained are likely to have wider implications for other environmental carcinogens. Other studies that have sought simple evidence, such as familial clustering or associations of lung cancer with blood group, HLA and other naturally occurring antigens, are also examined. The field of chromosomal abnormalities in lung cancer and the difficulties in interpreting them is reviewed only briefly, since this area may not directly relate to tobacco smoking and has been reviewed elsewhere (Birrer & Minna, 1988). Various sources of bias important in the interpretation of the metabolic studies in particular are outlined. Future research is likely to be dominated by the recent advances in molecular genetics that offer the possibility of circumventing bias by the direct identification of genes, but at present this is possible only to a limited extent. Familial clustering of lung cancer casesFamilial clustering of a cancer (or indeed of any disease) is an insensitive indicator of genetic predisposition. Peto (1980) and Bodmer (1986) have pointed out that a cancer can have a major genetic component yet show no detectable familial clustering. The ratio of the incidence of the cancer in relatives of known cases to that in age-matched controls is the only measure of familial clustering (in the absence of a marker). This ratio will be much smaller than the ratio of the incidence in genetically susceptible to non-susceptible individuals, which is the direct measure of the magnitude of the genetic effect. It is a question of dilution -not all patients with cancer will be genetically susceptible individuals, fewer of their relatives will be, and tne general population contains susceptibles as well as non-susceptibles. (1980) showed that even with a very large cancer risk in susceptibles, the incidence of cancer in relatives will generally be increased by no more than 1.5-3-fold. It is difficult in a family study to show that such a modest increase could not be due to chance, shared exposure or other bias.Five studies have examined lung cancer incidence in relatives of cases, but three (Tokuhata & Lilienfeld, 1963b;

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“…The between-individual variation in mutation frequency was 9-fold and the variation in binding levels of BzaP to DNA in the bronchial explants was 5-fold. Additional patients must be studied to determine if the variation in mutation frequency will eventually be as high (i.e., 75-fold) as the variation found in levels of BzaP bound to DNA in cultured bronchi from a large number of patients (17).…”

mentioning

confidence: 99%

“…When the metabolic rate of BzaP was estimated by measuring the formation of water-and organic-soluble metabolites, five bronchial explants (approximately [10][11][12][13][14][15][16][17][18][19][20] ;ig of mucosal DNA) metabolized BzaP at a rate similar to 2 X 106 x-irradiated Syrian golden hamster embryo cells (refs. 1 and 18; unpublished data).…”

mentioning

confidence: 99%