Showing papers by "Frederica P. Perera published in 1994"

Biomarkers of Environmental Tobacco Smoke in Preschool Children and Their Mothers

Abstract: BACKGROUND Adverse health effects attributable to environmental tobacco smoke (ETS) include respiratory illness and lung cancer in nonsmokers. There is accumulating evidence that children may be at heightened risk of cancer later in life as a result of exposure to carcinogens during their early development. It is of concern that as many as 9 million American children under the age of 5 years may be exposed to ETS. PURPOSE Our goal was to assess whether levels of cotinine and polycyclic aromatic hydrocarbon-albumin (PAH-albumin) are associated with ETS exposure in children and in women of reproductive age, after accounting for background exposures to PAHs in the diet, workplace, and the home environment. METHODS The study cohort was composed of 87 Hispanic and African-American mothers and 87 of their preschool children (2-5 years of age). Plasma cotinine was analyzed by gas chromatography; PAH-albumin adducts in peripheral blood were analyzed by enzyme-linked immunosorbent assay. Exposure data were obtained by interview-administered questionnaires. RESULTS Both cotinine and PAH-albumin were significantly higher in the children whose mothers smoked than in the children of nonsmoking mothers (P < .001 and P < .05, respectively). Among the children of nonsmoking mothers, cotinine levels were also significantly higher in those who had ETS exposure from others in the household compared with the unexposed children. By regression analysis, after adjustment for ethnicity, there was a significant dose-response relationship between cotinine and the number of cigarettes smoked per day by the mother, both in the children (partial r2 = .23; P = .01) and in the mothers (partial r2 = .22; P = .01). Among the nonsmoking mothers, regression of biomarkers against total passive smoking exposure also showed a significant association with cotinine (r2 = .25; P = .04). PAH-albumin did not show the same dose-related response with the smoking variables. Mothers' cotinine levels were significantly correlated with those of their children (r = .76; P < .001) as were PAH-albumin adducts (r = .27; P = .014). CONCLUSION ETS exposure of young children via their mothers' smoking is associated with increases not only in the internal dose of ETS (cotinine), which has been previously reported, but also in the biologically effective dose of the carcinogenic (PAH) components of ETS (PAH-albumin adducts). This observation underscores the carcinogenic and public health hazard of ETS. IMPLICATIONS Given the relatively low level of ETS exposure in this study, these results reinforce the need for effective programs aimed at smoking prevention and cessation among women, particularly women of reproductive age and minorities.

Polycyclic aromatic hydrocarbon-DNA adducts in smokers and their relationship to micronutrient levels and the glutathione-S-transferase M1 genotype.

Abstract: Sixty-three male cigarette smokers were entered into a cross-sectional study to determine whether inverse associations existed between polycyclic aromatic hydrocarbon (PAH)-DNA adduct levels and intake/serum levels of vitamin A, vitamin C and vitamin E. Associations between PAH-DNA adducts and intakes of carotene as well as serum levels of (β-carotene were also determined. Fasting blood samples were collected for assays of PAH-DNA adducts in circulating mononuclear cells, plasma cotinine and serum levels of vitamin A, β-carotene, vitamin C and vitamin E. Since genetic deficiency in the detoxifying enzyme glutathione S-transferase M1 (GSTM1) has been associated with increased risk of lung cancer, GSTM1 genotype was also determined. Analysis of PAH-DNA adducts by competitive enzyme-linked immunosorbent assay (ELISA) indicated that 70% of the subjects had detectable adducts with a mean of 4.38 adducts/108 nucleotides (range 1.00-24.1/108). Pearson’s method was utilized to determine whether any associations existed between the various host variables and PAH-DNA adducts. Previously, no significant associations were found between PAH-DNA adducts and cigarettes smoked/day, pack-years, daily/lifetime tar exposures or plasma cotinine levels [Carcinogenesis 13:2041,1992]. PAH-DNA adducts were inversely associated with serum cholesterol-adjusted vitamin E levels (r=-0.25, p≤0.05) and with smoking-adjusted vitamin C serum levels (r=-0.22, p<_0.09). Stratification by GSTM1 genotype indicated that these associations were limited to subjects with the null genotype. The relationship between adducts and serum cholesterol-adjusted vitamin E was significant in those of the null genotype (r=-0.38, p≤0.04) but not in those with the gene present (r=-0.12, p=0.5). Similarly, for smoking-adjusted vitamin C, the relationship with adducts was stronger in subjects with the null genotype (r=-0.35, p≤0.06) than in those with GSTM1 present (r=-0.05, p=0.77). These results are consistent with findings of prior epidemiological studies identifying significant inverse associations between antioxidant micronutrient status or GSTM1 genotype and the incidence of lung cancer. Additional studies should be conducted to confirm a possible protective role for vitamin E in PAH-DNA adduct formation and to explore further the possible roles of vitamin A, s-carotene and vitamin C in modulating adduct formation and lung cancer risk.

Platinum-DNA adducts assayed in leukocytes of patients with germ cell tumors measured by atomic absorbance spectrometry and enzyme-linked immunosorbent assay.

Abstract: Background. Platinum-DNA adducts can be measured in peripheral blood cells, and high adduct levels have previously been correlated with favorable clinical response to platinum-based therapy in patients with germ cell tumors and ovarian cancer. Methods. To evaluate the relationship between platinum-DNA adducts and clinical response to chemotherapy, 36 patients with germ cell tumors treated with cis-platin-based chemotherapy had platinum-DNA adducts assayed in leukocytes by atomic absorption spectrometry (AAS) and cisplatin-DNA enzyme-linked immunosorbent assay (ELISA). Three chemotherapy regimens were involved: cisplatin and etoposide (Regimen A); carboplatin and etoposide (Regimen B); and cyclophosphamide, vin-blastine, dactinomycin, bleomycin, and cisplatin [VAB-6] with or without high dose carboplatin plus etoposide plus autologous bone marrow rescue (Regimen C). Blood samples were drawn before and after each cycle of chemotherapy. Results. One hundred ninety-two blood samples were assayed by AAS and 137 by ELISA. DNA adducts measured by AAS and ELISA increased immediately after treatment and decreased during the intervening time before the next treatment. DNA adducts were measurable by both methods 4-8 weeks after the last cycle of therapy. The peak and mean adduct levels measured in samples drawn immediately after Cycles 1 and 2 and after all cycles were analyzed in terms of their relationship to clinical response. In contrast to numerous prior studies, a positive correlation was not observed between DNA adduct formation as determined by either AAS or ELISA and favorable clinical responses. Conclusions. This study demonstrated that peak and mean platinum-DNA adduct levels were influenced by the dose and schedule of the platinum analogue. For example, treatment with VAB-6 with or without high dose carboplatin and etoposide (Regimen C) resulted in significantly higher adduct levels when measured by AAS compared with Regimen A or B. Inconsistencies between studies regarding observed correlations of DNA adducts and treatment outcome may be attributable to differences in platinum analogue, dose, schedule, and timing of sample procurement. These factors must be considered in future studies. Cancer 1994; 73:2843–52.