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PubMed1997

The colchicine-binding and pyrene-excimer-formation activities of tubulin involve a common cysteine residue in the beta subunit.

Colchicine binding and pyrene excimer fluorescence of tubulin have been used to identify cysteine residue(s) essential for the colchicine binding activity of the protein. We report here that both the colchicine binding activity and the ability to form pyrene excimers of tubulin decay at an identical rate when the protein ages at 37 degrees C. Glycerol, which stabilizes the colchicine binding site also stabilizes the excimer formation equally. Thus, these two properties of tubulin are correlated and are likely to belong to the same structural domain. In an attempt to identify the excimer-forming Cys residues, we found that incubation of tubulin with N,N'ethylenebis(iodoacetamide) causes a significant inhibition of excimer fluorescence. Incubation of tubulin with colchicine prior to this treatment fully retains excimer-forming ability. It is known that Cys239 and Cys354 of beta-tubulin, which are about 0.9 nm apart in the native structure, are protected from ethylenebis(iodoacetamide) cross-linking by incubation of tubulin with colchicine [Luduena, R. F. & Roach, M. C. (1981) Pharmacol. Ther. 49, 133-152]. These residues must therefore be responsible for the excimer formation of tubulin with pyrene maleimide. Incubation of tubulin with ethylenebis(iodoacetamide) decreases the colchicine binding activity and the excimer formation at an identical rate. Since the alkylation of Cys239 of beta-tubulin (responsible for tubulin self-assembly) has no effect on colchicine binding [Bai, R., Lin, C. M., Nguyen, N. Y., Liu, T. & Hamel, E. (1989) Biochemistry 28, 5606-5612], our results suggest that excimer formation and the colchicine binding site of tubulin share Cys354 of the beta-subunit. Determination of the number of essential Cys residue(s) for colchicine binding activity, using the statistical method of Tsou [Tsou, C. L. (1962) Sci. Sin. 11, 1535-1558], also shows only one essential Cys residue.

Animals↗
PubMed1993

Mechanisms of quenching of the fluorescence of a benzo[a]pyrene tetraol metabolite model compound by 2'-deoxynucleosides.

The hydrophobic interactions of bulky polycyclic aromatic hydrocarbons with nucleic acid bases and the formation of noncovalent complexes with DNA are important in the expressions of the mutagenic and carcinogenic potentials of this class of compounds. The fluorescence of the polycyclic aromatic residues can be employed as a probe of these interactions. In this work, the interactions of the (+)-trans stereoisomer of the tetraol 7,8,9,10-tetrahydroxytetrahydrobenzo[a]pyrene (BPT), a hydrolysis product of a highly mutagenic and carcinogenic diol epoxide derivative of benzo[a]pyrene, were studied with 2'-deoxynucleosides in aqueous solution by fluorescence and UV spectroscopic techniques. Ground-state complexes between BPT and the purine derivatives 2'-deoxyguanosine (dG), 2'-deoxyadenosine (dA), and 2'-deoxyinosine (dI) are formed with association constants in the range of approximately 40-130 M(-1). Complex formation with the pyrimidine derivatives 2'-deoxythymidine (dT), 2'-deoxycytidine (dC), and 2'-deoxyuridine (dU) is significantly weaker. Whereas dG is a strong quencher of the fluorescence of BPT by both static and dynamic mechanisms (dynamic quenching rate constant k(DYN) = [2.5 +/- 0.4] x 10(9) M(-1)s(-1), which is close to the estimated diffusion-controlled value of approximately 5 x 10(9) M(-1)s(-1), both dA and dI are weak quenchers and form fluorescence-emitting complexes with BPT. The pyrimidine derivatives dC, dU, and dT are efficient dynamic fluorescence quenchers (k(DYN) approximately [1.5-3.0] x 10(9) M (-1)s(-1), with a small static quenching component due to complex formation evident only in the case of dT. None of the four nucleosides dG, dA, dC and dT are dynamic quenchers of BPT in the triplet excited state; the observed lower yields of triplets are attributed to the quenching of single excited states of BPT by 2'-deoxynucleosides without passing through the triplet manifold of BPT. Possible fluorescence quenching mechanisms involving photoinduced electron transfer are discussed. The strong quenching of the fluorescence of BPT by dG, dC and dT accounts for the low fluorescence yields of BPT-native DNA and of pyrene-DNA complexes.

Benzo(a)pyrene↗
PubMed1995

Nucleic acid hybridization accompanied with excimer formation from two pyrene-labeled probes.

We developed a novel nucleic acid hybridization method based on excimer formation. We used two different 16-mer oligonucleotide probes that had a combined continuous-sequence run that was complementary to a target 32-mer. Prior to hybridization, the adjacent terminal ends (i.e. the 3'-terminal of one probe and the 5'-terminal of the other probe) were each labeled with one pyrene residue. When these probes simultaneously hybridized to the target, a 495 nm broad fluorescence band was produced. The intensity of this band increased as the intensity of the pyrene monomer bands decreased, indicating that the 495 nm band was attributed to the pyrene excimer. The excimer fluorescence, easily differentiated from the monomer bands for emission wavelength, opens up a new way to perform homogeneous hybridization assays and in vivo imaging of nucleic acids.

Base Sequence↗
PubMed2001

Mycobacterium diversity and pyrene mineralization in petroleum-contaminated soils.

Degradative strains of fast-growing Mycobacterium spp. are commonly isolated from polycyclic aromatic hydrocarbon (PAH)-contaminated soils. Little is known, however, about the ecology and diversity of indigenous populations of these fast-growing mycobacteria in contaminated environments. In the present study 16S rRNA genes were PCR amplified using Mycobacterium-specific primers and separated by temperature gradient gel electrophoresis (TGGE), and prominent bands were sequenced to compare the indigenous Mycobacterium community structures in four pairs of soil samples taken from heavily contaminated and less contaminated areas at four different sites. Overall, TGGE profiles obtained from heavily contaminated soils were less diverse than those from less contaminated soils. This decrease in diversity may be due to toxicity, since significantly fewer Mycobacterium phylotypes were detected in soils determined to be toxic by the Microtox assay than in nontoxic soils. Sequencing and phylogenetic analysis of prominent TGGE bands indicated that novel strains dominated the soil Mycobacterium community. Mineralization studies using [(14)C]pyrene added to four petroleum-contaminated soils, with and without the addition of the known pyrene degrader Mycobacterium sp. strain RJGII-135, indicated that inoculation increased the level of degradation in three of the four soils. Mineralization results obtained from a sterilized soil inoculated with strain RJGII-135 suggested that competition with indigenous microorganisms may be a significant factor affecting biodegradation of PAHs. Pyrene-amended soils, with and without inoculation with strain RJGII-135, experienced both increases and decreases in the population sizes of the inoculated strain and indigenous Mycobacterium populations during incubation.

Biodegradation, Environmental↗
PubMed2001

Effects of tobacco smoke and benzo[a]pyrene on human endothelial cell and monocyte stress responses.

Smoking is an important risk factor for atherosclerosis. We compared tobacco smoke filtrate with benzo[a]pyrene (a prominent xenobiotic component of tobacco smoke) for the capacity to induce stress proteins and cause cell death in human monocytes and vascular endothelial cells, two cell types that are involved in the formation of atherosclerotic lesions. Exposure to freshly prepared filtrates of tobacco smoke induced in both monocytes and endothelial cells expression of the inducible heat shock protein (HSP)70 and heme oxygenase-1 (HO-1) and produced loss of mitochondrial membrane potential. Later, cell death by apoptosis or necrosis occurred depending on the concentration of tobacco smoke. These toxic effects could be prevented by the antioxidant N-acetylcysteine. In contrast, exposure of these cells to benzo[a]pyrene alone evoked neither stress proteins nor mitochondrial damage but did induce cell death by necrosis. Thus our results indicate that tobacco smoke rapidly induces complex oxidant-mediated stress responses in both vascular endothelial cells and circulating monocytes that are independent of the benzo[a]pyrene content of the smoke.

Acetylcysteine↗
PubMed1989

Pyrene-methyl lauryl ester, a new fluorescent substrate for lipases: use for diagnosis of acid lipase deficiency in Wolman's and cholesteryl ester storage diseases.

Fluorescent pyrene-methyl lauryl ester (PMLes) was synthesized and used for the determination of cellular lipase activities in lymphoblasts and fibroblasts from normal subjects and from patients affected with Wolman's or cholesteryl ester storage diseases (both exhibiting a deficiency of the lysosomal acid lipase). The hydrolysis of PMLes by acid lipase could be followed directly in a spectrofluorometer; this was possible because of the very high fluorescence emission of pyrene-methanol at 378 nm (monomeric form) in aqueous medium, whereas the substrate has practically no monomeric emission at 378 nm but emits only at 475 nm (excimeric form) in the experimental conditions used: this property permitted us to use PMLes as a fluorogenic substrate. In an alternative procedure, the enzymatic reaction could be determined after partition of the reaction mixture in a biphasic system of heptane and aqueous ethanol; the residual undegraded substrate partitioned into the upper heptane phase and the fluorescence of the product (i.e. pyrene-methanol) was read in the lower aqueous-ethanolic phase, at 378 nm. PMLes was hydrolyzed in extracts of normal lymphoblasts and fibroblasts by at least two lipases, one acidic lipase (pH 4.0) and a second more neutral enzyme (pH 6.5). The acidic lipase activity was practically absent in lymphoblasts and fibroblasts from Wolman's or cholesteryl ester storage diseases. This demonstrates that the fluorescent PMLes is hydrolyzed by the lysosomal acid lipase and can be used as a very sensitive fluorogenic substrate which permits direct recording of product formation and is suitable for the enzymatic diagnosis of either of these diseases.

Cell Line↗
PubMed1987

Microspectrofluorometric comparison of benzo(a)pyrene and dibenzo(c,h)acridine metabolism in single living 3T3 fibroblasts.

The purpose of this study was to determine if dibenzo(c,h)acridine could be used as a probe for the N-heterocyclic aromatic compound detoxification system. The determination was achieved by cell population studies (histograms) using microspectrofluorimetry on single living cells. The results show a similar metabolic distribution pattern between dibenzo(c,h)acridine and benzo(a)pyrene, whereas important differences appear between 6-aminochrysene and dibenzo(c,h)acridine, respectively amine aromatic and N-heterocyclic aromatic compounds. No differences were observed in the metabolism of benzo(a)pyrene in untreated cells and those treated with constant concentrations of dibenzo(c,h)acridine. However, inhibition of dibenzo(c,h)acridine metabolism was observed in the presence of benzo(a)pyrene, indicating that this compound should be a preferential substrate for a cell detoxification system.

Acridines↗
PubMed1983

Study of the cell-transforming ability of amosite and crocidolite asbestos and the ability to induce changes in the metabolism and macromolecular binding of benzo(a)pyrene in C3H10T1/2 cells.

The cell transforming ability of asbestos dusts was investigated using C3H10T1/2 murine fibroblasts. In a series of experiments, crocidolite and amosite caused no increase in the number of transformed colonies over that seen in cultures from untreated cells. The dusts were, however, capable of augmenting the oncogenic effect of benzo(a)pyrene. This synergistic effect was evident when fibers and chemicals were added to cultures as simple mixtures and when benzo(a)pyrene was adsorbed to the surface of fibers. Asbestos dust did not, however, appear to exert its oncogenic enhancing effect by modifying the metabolism of benzo(a)pyrene in C3H10T1/2 cells.

Animals↗
PubMed1994

Effects of sulfite on the uptake and binding of benzo[a]pyrene diol epoxide in cultured murine respiratory epithelial cells.

Sulfur dioxide (SO2) may act as a cocarcinogen with benzo[a]pyrene (BaP) in the respiratory tract. We have modeled this effect by examining the interactions of 7r,8t-dihydroxy-9t,10t-epoxy-7,8,9,10-tetrahydrobenzo[a]pyrene (anti-BPDE) with sulfite, the physiological form of SO2, in a murine respiratory epithelial cell line (C10). We exposed C10 cells to [3H]-anti-BPDE and determined the effects of 1 and 10 mM sulfite on the uptake and subcellular localization of labeled products. Autoradiographic analysis showed that sulfite doubled the nuclear localization of anti-BPDE-derived materials after a 4-hr incubation period. The net nuclear localization of anti-BPDE-derived materials was not affected by sulfite during the first 60 min, but nuclear localization continued to increase in the sulfite-containing incubations throughout the 4-hr incubation period. Little increase in nuclear localization of anti-BPDE-derived material was noted in the incubations without sulfite after 60 min. Subcellular fractionation was performed to determine the amount of label associated with cytosolic and nuclear fractions and to determine covalent binding to protein and DNA. Sulfite produced a modest increase in the amount of [3H]-anti-BPDE-derived products bound to protein; however, binding to nuclear DNA increased by more than 200% with 10 mM sulfite. Analysis of the supernatants from the cytosolic and nuclear fractions of cells exposed to anti-BPDE and sulfite demonstrated the presence of 7r,8t,9t-trihydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene-10c-su lfonate (BPT-10-sulfonate). [3H]-BPT-10-sulfonate was unable to enter C10 cells, suggesting that it is formed intracellularly.(ABSTRACT TRUNCATED AT 250 WORDS)

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMedDate not supplied

Atmospheric carcinogens in Rio de Janeiro during the summer of 1998/99: benzo[a]pyrene and benzene.

Rio de Janeiro, the second largest city in Brazil, is affected by severe pollution episodes and presents a high respiratory cancer incidence in comparison with the rest of the country. To monitor atmospheric pollution during the summer of 1998/1999 and to estimate the impact of organic pollution on public health, we determined the levels of two carcinogenic organic chemicals, benzo[a]pyrene and benzene, in four distinct sites throughout the city. A review of the levels recorded in other urban areas worldwide during the last ten years indicates that the benzo[a]pyrene (< or = 0.70 ng/m3) and benzene (< or = 11 micrograms/m3) concentrations found in Rio are relatively low. The highest levels were generally recorded in developing Asian countries, whereas the lowest values were found in North America. Unlike urban areas in temperate zones, pollution derived from domestic heating is minor in Rio de Janeiro, where most of the benzo[a]pyrene and benzene pollution originates from vehicular traffic. The quite distinct fuels used in light-duty vehicles in Brazil, combined with strong light incidence and increased rainfall during the summer, also contribute to diminish the levels of such pollutants.

Air Pollution↗
PubMed2003

Selectivity and efficiency of pyrene attachment to alkanes induced by broadband X-rays.

Bombardment of pyrene-doped n-heneicosane (C21H44) in its orthorhombic solid phase with <1.3> MeV broadband X-rays results in the formation of both mono- and di-heneicosylpyrenes, whereas the same dose in liquid cyclohexane yields only monosubstituted pyrene. In both cases, the reaction efficiency decreases as pyrene concentration is increased from 10-5 to 10-2 M. Qualitatively, the overall attachment efficiency is higher in orthorhombic n-heneicosane than in liquid cyclohexane, but the selectivity of attachment is greater in cyclohexane. Differences between these results and those from irradiations of the same samples with eV range photons are discussed.

Alkanes↗
PubMed2004

Cell-specific CYP1A expression and benzo[a]pyrene adduct formation in gills of rainbow trout (Oncorhynchus mykiss) following CYP1A induction in the laboratory and in the field.

The effect of cytochrome P4501A (CYP1A) induction on cell-specific benzo[a]pyrene (BaP) adduct formation was studied in rainbow trout (Oncorhynchus mykiss) gills. Fish preexposed to beta-naphthoflavone (betaNF) or caged in a polluted river were exposed to waterborne 3H-benzo[a]pyrene (3H-BaP). The 3H-benzo[a]pyrene adducts in the gill filaments were localized by autoradiography and CYP1A protein by immunohistochemistry. Ethoxyresorufin O-deethylase (EROD) activity was measured using a gill filament-based ex vivo assay. Branchial 3H-BaP binding and EROD activity were enhanced by exposure to betaNF or to the river water, and completely blocked by the CYP1A inhibitor ellipticine. The predominant sites of adduct formation were in epithelium of the secondary lamellae and in epithelium of the efferent edge of the gill filament. In betaNF-exposed fish, the strongest CYP1A immunoreactivity was observed in differentiating cells and in pillar cells. In fish caged in the polluted river, strong CYP1A immunoreactivity was found in most cells in the secondary lamellae, whereas the primary lamellae were almost devoid of immunoreactivity. Our results reveal a discrepancy between the localization of CYP1A protein and BaP adducts in the gill. Consequently, other factors, such as bioavailability of waterborne polycyclic aromatic hydrocarbons (PAHs) to the target cells, are important for the localization of PAH adducts in the gill.

Animals↗
PubMed2006

Pyrene-appended alpha-cyclodextrin as a fluorescent pH probe responding to a wide range.

Pyrene-appended alpha-cyclodextrin (3) in which a trimethylenediamine linker connected the pyrene residue to the alpha-cyclodextrin moiety showed pH-dependent fluorescence intensity changes. The fluorescence intensity was almost linearly changed within the pH range of 5 - 10. The unique fluorescence response of 3 to the pH was due not only to the favorable pK(a) values (pK(a1) = 6.4 and pK(a2) = 8.8), but also to the almost equal contributions of the amino groups to the pyrene's fluorescence quenching.

Diamines↗
PubMed1988

Metabolism and cytotoxicity of benzo(a)pyrene in the human lung tumour cell line NCI-H322.

1. The human lung tumour cells NCI-H322 metabolized benzo(a)pyrene (BP) at a rate of 160 pmol/10(6) cells/h for at least 8 h. About 30% of the total metabolites were water-soluble, 30% of which were conjugates with glutathione. The water-soluble fraction also contained BP sulphates but no BP glucuronides. 2. The cytotoxic potency of BP and its metabolites, 3-hydroxybenzo(a)pyrene (3-OH-BP) and (+/-) anti-7,8-dihydroxy-7,8-dihydrobenzo(a)pyrene (7,8-diol-BP), differed by an order of magnitude with the ranking 7,8-diol-BP greater than BP greater than 3-OH-BP. The cytotoxicity of BP was not detected at the end of a 24 h treatment period but became increasingly apparent at later times. In contrast, the cytotoxicity of 3-OH-BP was observed immediately after the treatment period and did not increase greatly thereafter. 7,8-Diol-BP caused both 'immediate' and 'late' effects. 3. The time course and concentration dependence suggested that the cytotoxicity of BP in NCI-H322 cells was not attributable to the formation of 3-OH-BP, but more likely resulted from the formation of other products such as 7,8-diol-BP.

Animals↗
PubMed2005

Ultraviolet radiation increases the toxicity of pyrene, 1-aminopyrene and 1-hydroxypyrene to human keratinocytes.

Over the past several years, a great deal of interest has been focused on the harmful effects of ultraviolet (UV) radiation to human skin. UV light has been implicated in aging, sunburn and skin cancer. Few studies, however, have been done to determine the effects that UV light, in conjunction with other environmental contaminants, may have on human skin. Polycyclic Aromatic Hydrocarbons (PAHs) are a class of compounds that have been reported to be toxic, mutagenic and carcinogenic to many eukaryotic organisms. UV light is also known to increase the toxicity of PAHs through photo-activation and photo-modification. The purpose of this study was to assess the effects of UV-A irradiated pyrene (Pyr), 1-aminopyrene (1-AP) and 1-hydroxypyrene (1-HP) on human keratinocytes, the skin primary site of UV irradiated PAH exposure. Our findings indicate that simultaneous treatment of human keratinocyte cell line, HaCaT, with 1.0 microg/ml pyrene, 1-AP or 1-HP and 3.9 J/cm2/min UV-A light resulted in significant inhibition of cell proliferation. Approximately 100% of the cells died in the case of UV-A irradiated 1-AP and 1-HP. In the case of UV-A irradiated pyrene, more than 70% of the cells died, indicating that UV-A is able to transform these PAHs into more harmful intermediates.

Cell Line↗
PubMed1999

Differential protection against benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide-induced DNA damage in HepG2 cells stably transfected with allelic variants of pi class human glutathione S-transferase.

The pi class glutathione S-transferase (GSTP1-1), which is polymorphic in human populations, is believed to play an important role in detoxification of the ultimate carcinogen of widespread environmental pollutant benzo[a]pyrene [(+)-anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide [(+)-anti-BPDE]]. The allelic variants of human GSTP1-1 (hGSTP1-1) differ in their structures by the amino acids in positions 104 (isoleucine or valine) and/or 113 (valine or alanine). Here, we have determined the protective effect of overexpression of allelic variants of hGSTP1-1, through stable transfection in HepG2 cells, against (+)-anti-BPDE-induced DNA modification. Clonal transfectants of HepG2 cells corresponding to the three allelic variants of hGSTP1-1 [(I104,A113), (V104,A113), and (V104,V113), denoted hGSTP1(IA), hGSTP1(VA), and hGSTP1(VV), respectively] with similar levels of hGSTP1 protein were identified and characterized for their GST activity and (+)-anti-BPDE-induced DNA modification. The glutathione S-transferase activity toward (+)-anti-BPDE was significantly higher (approximately 3.0-3.6-fold) in cells transfected with hGSTP1(VA) [HepG2(VA)] and hGSTP1(VV) [HepG2(VV)] compared with hGSTP1(IA) transfectant [HepG2(IA)]. The formation of (+)-anti-BPDE-DNA adducts was significantly reduced in HepG2(VA) and HepG2(VV) cells compared with cells transfected with insert-free vector (HepG2-vect). Maximum protection against (+)-anti-BPDE-induced DNA damage was afforded by the hGSTP1(VV) isoform. The results of this study indicate that the allelic variants of hGSTP1-1 significantly differ in their ability to provide protection against (+)-anti-BPDE-induced DNA damage. Thus, hGSTP1-1 polymorphism may be an important factor in differential susceptibility of individuals to tumorigenesis induced by benzo[a]pyrene.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed1999

Effects of aflatoxin B1 on the hepatic microsomal mixed function oxidase system during phenobarbital and benzo(a)pyrene treatment in chickens.

Administration of 1.5 mg aflatoxin B1 (AFB1)/kg in DMSO as a single i.p. dose to 80 mg phenobarbital/kg i.p. for 3 d pretreated chickens showed significant decrease in the levels of electron transport components and drug metabolizing enzymes compared to phenobarbital administration alone. Induction of mixed function oxidase enzymes due to phenobarbital was not affected by the AFB1 pretreatment. AFB1 administration to 20 mg benzo(a)pyrene/kg in safflower seed oil i.p. for 2 d pretreated chickens showed significant decrease in cytochrome b5 and drug metabolizing enzymes when compared with benzo(a)pyrene treatment alone. However, cytochrome P450 level was slightly higher due to administration of AFB1 to benzo(a)pyrene-injected chickens. The results indicate that the phenobarbital-induced cytochrome P450 is more susceptible to AFB1 than benzo(a)pyrene-induced cytochrome P450.

Aflatoxin B1↗
PubMed2001

Sensitivity to DNA damage induced by benzo(a)pyrene diol epoxide and risk of lung cancer: a case-control analysis.

Levels of DNA adducts vary greatly in vivo, attributable to individual differences in enzymatic bioactivation of benzo(a)pyrene. We developed an assay to measure the levels of DNA adducts induced in vitro by benzo(a)pyrene diol epoxide (BPDE), a bioactivated form of benzo(a)pyrene. In this large molecular epidemiological study of lung cancer, we tested the hypothesis that the level of in vitro BPDE-induced adducts is associated with risk of lung cancer. This hospital-based case-control study included 221 newly diagnosed lung cancer cases and 229 healthy controls frequency matched on age, sex, ethnicity, and smoking status. Short-term cultured peripheral blood lymphocytes from each subject were exposed in vitro to BPDE (4 microm) for 5 h, and the 32P-postlabeling method was then used to measure BPDE-induced DNA adducts in the host cells. Overall, the patients had significantly higher levels of BPDE-DNA adducts than did the controls (mean +/- SD per 107 nucleotides, 93.2+/-89.3 for cases versus 63.7+/-61.1 for controls; P = 0.001). Univariate and multivariate logistic regression analyses were performed to calculate the crude and adjusted odds ratios and their 95% confidence intervals. When the median adduct level of controls (46/10(7) nucleotides) was used as the cutoff point, 64% of cases had higher levels (odds ratio, 2.15; 95% confidence interval, 1.39-3.33, adjusted for age, sex, ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer). Stratified analyses showed consistently higher levels of BPDE-induced adducts in cases than in controls, regardless of subgroup of age, sex, ethnicity, body mass index, recent weight loss, pack-years smoked, smoking in the last 24 h, and family history of cancer. A significant dose-response relationship between the quartile levels of BPDE-induced DNA adducts and the risk of lung cancer was observed (trend test, P < 0.001). The significant association between the level of in vitro BPDE-induced DNA adducts and risk for lung cancer suggests that subjects very sensitive to BPDE-induced DNA damage may have a suboptimal ability to remove the BPDE-DNA adducts and so are susceptible to tobacco carcinogen exposure and, therefore, may be at increased risk of lung cancer.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗