Relationship between environmental tobacco smoke exposure and carcinogen-hemoglobin adduct levels in nonsmokers.

BACKGROUND: A potent bladder carcinogen for workers in the dye industry, 4-aminobiphenyl (4-ABP), is present in environmental tobacco smoke and has been shown to bond covalently with hemoglobin. PURPOSE: The goal of this study was to examine the relationship between exposure to environmental tobacco smoke and levels of 4-ABP-hemoglobin adducts in nonsmoking pregnant women and to compare adduct levels in those women with levels in smoking pregnant women. METHODS: A questionnaire on smoking and exposure to environmental tobacco smoke was administered to 15 pregnant women who smoked cigarettes and 40 who did not smoke. Exposure was quantified for 1 week with a personal diary and by air sampling with a monitor worn by each woman. The monitor collected nicotine by passive diffusion to a filter treated with sodium bisulfate, and the deposit on the filter was analyzed by gas chromatography. Aliquots of maternal blood and cord blood collected during delivery were analyzed for 4-ABP-hemoglobin adducts by gas chromatography with negative ion chemical ionization mass spectrometry. RESULTS: The mean adduct level in smokers (184 pg of 4-ABP per gram of hemoglobin) was substantially higher than that in nonsmokers (22 pg/g). This difference was statistically significant. Among nonsmokers, the levels of 4-ABP adducts increased significantly with increasing environmental tobacco smoke level (P = .009). Those in the lowest exposure category (< 0.5 micrograms/m3 weekly average nicotine) had median 4-ABP-hemoglobin adduct levels of 15 pg of 4-ABP per gram of hemoglobin, while those in the highest exposure category (> or = 2.0 micrograms/m3) had median levels of 26 pg/g. Nonsmokers in this study had a median adduct level of 20 pg/g, and smokers had a median level of 143 pg/g. CONCLUSIONS: 4-ABP-hemoglobin adduct levels in nonsmokers were 14% of the levels in smokers, which is consistent with findings of 20% in two other studies. Nonsmokers may receive a nontrivial dose of carcinogens from environmental tobacco smoke proportional to their exposure to environmental tobacco smoke. IMPLICATION: The relationship between environmental tobacco smoke exposure and 4-ABP-hemoglobin adduct levels supports epidemiologic evidence that environmental tobacco smoke is carcinogenic to passive smokers.

4-Aminobiphenyl hemoglobin adducts in fetuses exposed to the tobacco smoke carcinogen in utero.

Maternal-fetal exchange of a potent tobacco-related human carcinogen, 4-aminobiphenyl, was studied in smoking (n = 14) and nonsmoking (n = 38) pregnant women. N-Hydroxy-4-aminobiphenyl, the active metabolite of 4-aminobiphenyl, forms chemical addition products (adducts) with hemoglobin. Levels of 4-aminobiphenyl hemoglobin adducts were measured in maternal-fetal paired blood samples obtained from smoking and nonsmoking women during labor and delivery. Carcinogen-hemoglobin adducts were detected in all maternal and fetal blood samples. Levels of such adducts were significantly higher (P less than .001) in maternal and fetal blood samples from smokers: the mean 4-aminobiphenyl hemoglobin adduct level was 92 +/- 54 pg/g of hemoglobin in blood samples from fetuses of smokers, and 17 +/- 13 pg/g of hemoglobin in blood samples from fetuses of nonsmokers; the mean maternal 4-aminobiphenyl hemoglobin adduct level was 183 +/- 108 pg/g of hemoglobin in smokers, and 22 +/- 8 pg/g of hemoglobin in nonsmokers. Fetal carcinogen-adduct levels were consistently lower than maternal levels: the mean maternal to fetal ratio was 2.4 +/- 1.1 in smokers and 1.9 +/- .98 in nonsmokers. Fetal 4-aminobiphenyl hemoglobin adduct levels were strongly associated (correlation coefficient [r2] = .51, P = .002) with maternal 4-aminobiphenyl hemoglobin adduct levels when paired samples from smoking mothers were analyzed. A measure of third-trimester tobacco smoke exposure based on number of cigarettes smoked per day, amount of each cigarette smoked, and depth of inhalation was associated (r2 = .59, P = .029) with maternal 4-aminobiphenyl levels but not with fetal 4-aminobiphenyl levels. This study demonstrates that a potent tobacco-related carcinogen, 4-aminobiphenyl, or its active metabolite, N-hydroxy-4-aminobiphenyl, crosses the human placenta and binds to fetal hemoglobin in concentrations that are significantly higher in smokers than in nonsmokers.

Population-based medical education: linkages between schools of medicine and public health agencies.

PURPOSE: To examine the educational linkages between medical schools and public health agencies (PHAs); characterize programs for medical student placement at PHAs; explore attitudes toward using PHAs as student teaching sites; and investigate factors that facilitate or hinder such placements. METHOD: A 20-item questionnaire was mailed in the summer of 1994 to all 134 allopathic medical schools in the United States (for schools with more than one campus, each campus was counted as a separate school). The chi-square and Mann-Whitney U tests were used to assess associations between variables. RESULTS: A total of 108 schools (81%) responded. Of these, 68 (63%) reported having a program that places some or all students at PHAs. The most common facilitating factors were proximity of PHA(s) (84%), faculty interest in public health (76%), support of the PHA director and personnel (67%), and faculty appointments for public health personnel (63%). Two barriers differentiated schools having a PHA placement program from those not having one: lack of faculty interest (p = .001) and lack of a designated PHA contact person (p = .002). CONCLUSION: An unexpectedly large number of schools placed students in PHAs to receive training. However, medical schools are not utilizing the full potential of PHAs as teaching sites.

Office systems for promoting screening mammography. A survey of primary care practices.

BACKGROUND: Office tracking, scheduling, and reminder systems have been shown to improve utilization of screening mammography, but little is known about the use of these systems by primary care physicians. METHODS: We surveyed 132 primary care and obstetrics and gynecology practices affiliated with an independent practice association model health maintenance organization in central Massachusetts to determine their use of reminder, scheduling, and follow-up systems, and education and counseling services aimed at increasing screening mammography rates. RESULTS: The use of chart flags to remind physicians of a patient's need for mammography screening was reported by 30% of practices. Thirty-one percent reported the use of flow sheets, and 27% reported the use of mail or telephone patient reminders. At least one of these three systems was used by 57% of the practices, whereas 43% reported having none of these three systems. Variations in the use of these office systems were related to specialty type, physician number, and clinical staffing. The majority of practices (77%) reported using written educational materials, and 42% offered prevention counseling with nonphysician staff. Very few offices (8%) reported using mail or telephone reminders for previously scheduled appointments. CONCLUSIONS: Despite the proven effectiveness of reminder systems for screening mammography, many practices do not have a system in place. Promotion of reminder systems in primary care practices could have a substantial impact on mammography utilization.

Development of epidemiologic tools for measuring environmental tobacco smoke exposure.

In this study, current weekly environmental tobacco smoke exposure was measured in 53 nonsmoking volunteers. Three exposure assessment tools were used: a passive nicotine monitor; a baseline questionnaire; and a seven-day diary. Exposure episodes were recorded according to location, space ventilation characteristics, number of smokers, number of hours, proximity of smokers, and intensity of environmental tobacco smoke. In Phase 1, various formulas for an environmental tobacco smoke exposure index based on the questionnaires and diaries of 19 volunteers were tested against the nicotine (microgram) collected by the monitor to determine the index providing the best fit. The formula referred to as the hsp (hours x smokers x proximity) index provided the best correlation with log nicotine levels for the questionnaire (r2 = 0.829) and the diary (r2 = 0.900). All episodes of environmental tobacco smoke exposure in all locations were summed over seven days. Each exposure received a weighting according to number of hours (h), number of smokers (s) and proximity of smokers (p). In Phase 2, the hsp index was refined to adjust for social situations with many smokers. In Phase 3, the refined hsp index (hsp*) was used to predict cumulative weekly nicotine collected on monitors worn by 33 new volunteers. All 33 nicotine measurements in the validation set were closely predicted by a simple linear regression model using log nicotine and the hsp* index (r2 = 0.98). The results of this study indicate that relatively simple questionnaires and diaries can be developed to assess current environmental tobacco smoke exposure for epidemiologic studies.

Identification of an in vivo chrysene diol epoxide adduct in human hemoglobin.

Human blood samples were analyzed by fluorescence and mass spectrometry for the presence of polycyclic aromatic hydrocarbon metabolites covalently bound to hemoglobin. Globin was prepared by HCl-acetone precipitation and enzymatically digested. The polycyclic aromatic alcohols generated from ester adducts during digestion were concentrated by monoclonal antibody immunoaffinity chromatography and separated by C-18 HPLC. Analysis of collected fractions by room temperature fluorescence spectroscopy revealed the presence of the anti-tetrahydrotetrols of benzo[a]pyrene and another component possessing a phenanthrene chromophore. Gas chromatographic-mass spectral analysis of the HPLC fractions revealed that the latter compound was r-1,t-2,t-3,c-4-tetrahydroxy-1,2,3,4-tetrahydrochrysene, arising from a hemoglobin-chrysene diol epoxide adduct.