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Biomedical subjects

M S Wolff

Publications and source records attributed to M S Wolff.

At least 19 recordsLinked to original sources
PubMed2000

Risk of breast cancer and organochlorine exposure.

A prospective investigation of breast cancer and organochlorine (OC) exposures was undertaken in the New York University Women's Health Study. Cases (n = 148) and individually matched controls (n = 295) were identified among women whose blood had been obtained 6 months or more prior to breast cancer diagnosis. In addition, among 84 cases and 196 controls, two or more consecutive annual blood samples were available to estimate half-lives of 1,1-dichloro-2,2-bis(p-chlorophenyl) ethene (DDE) and polychlorinated biphenyls (PCBs). Cases and controls had similar levels of DDE (geometric mean, 6.95 versus 7.27 ng/ml; lipid-adjusted geometric mean, 977 versus 1100 ng/g) and PCBs (5.04 versus 4.97 ng/ml; lipid-adjusted geometric mean, 683 versus 663 ng/g). These differences remained nonsignificant when estrogen receptor status of tumors was considered. DDE and PCB half-lives did not differ in case versus control patients. In control patients, DDE and PCB half-lives were strongly correlated (r(s) = 0.71), and the half-life of DDE (but not that of PCB) was inversely correlated with body mass index (BMI), yet the blood serum levels of PCB (but not those of DDE) were correlated with BMI. We conclude that there is no evidence for an association of breast cancer risk with DDE or PCB levels in blood (based on samples collected during the period 1987-1992) nor with their elimination half-lives. However, changes in DDE and PCBs over time are influenced by metabolism, BMI, and current OC exposures, and each may affect interpretation of OC levels in risk assessment models.

Adult↗
PubMed1999

The effect of ammonium glycopyrrolate (Robinul)-induced xerostomia on oral mucosal wetness and flow of gingival crevicular fluid in humans.

The antisialogogue, ammonium glycopyrrolate (Robinul), was used to reduce the salivary flow rate in healthy individuals with normal salivary function to determine whether the dry-mouth symptoms and reduced amounts and patterns of oral mucosal wetness found previously in hyposalivators could be induced by this means. After baseline measurements, the drug was given to 10 healthy volunteers and their resting whole-saliva flow rate was measured at 0, 15, 60, 105 and 150 min thereafter. At the same times, the thickness of the layer of residual mucosal saliva (a measure of residual mucosal wetness) at each of 22 intraoral sites was also determined. The saliva flow rate fell from a mean of 0.45 +/- 0.07 ml/min to a mean of 0.05 +/- 0.02 ml/mm by 1 h and slowly thereafter to a mean of 0.02 +/- 0.01 to 0.03 +/- 0.01 ml/min for the remainder of the experiment. Onset of dryness symptoms was observed approx. 30 min after giving the drug. Simultaneously, the residual saliva at each of the 22 sites teted decreased to a thickness level previously found in patients with hyposalivation and who exhibited an intense feeling of dry mouth. Despite these decreases in thickness, the pattern of residual mucosal wetness throughout the mouth remained more or less unchanged. As in earlier studies, wetness was least on the hard palate and highest on the posterior dorsum of the tongue. An altered taste of the residual saliva in the mouth and an increased feeling of roughness as the tongue was passed over labial and buccal mucosal surfaces were noted. The amount of gingival crevicular fluid (GCF) in 12 gingival sites in each of the participants was also measured. Unlike the reduction in salivary flow, changes in GCF over the 150 min of the study were negligible. From this it was concluded that GCF could contribute much more to the oral fluids in dry-mouth than in normal individuals, especially when there is greater gingival inflammation.

Adult↗
PubMed1999

Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line.

Estrogens, whether natural or synthetic, clearly influence reproductive development, senescence, and carcinogenesis. Pyrethroid insecticides are now the most widely used agents for indoor pest control, providing potential for human exposure. Using the MCF-7 human breast carcinoma cell line, we studied the estrogenic potential of several synthetic pyrethroid compounds in vitro using pS2 mRNA levels as the end point. We tested sumithrin, fenvalerate, d-trans allethrin, and permethrin. Nanomolar concentrations of either sumithrin or fenvalerate were sufficient to increase pS2 expression slightly above basal levels. At micromolar concentrations, these two pyrethroid compounds induced pS2 expression to levels comparable to those elicited by 10 nM 17ss-estradiol (fivefold). The estrogenic activity of sumithrin was abolished with co-treatment with an antiestrogen (ICI 164,384), whereas estrogenic activity of fenvalerate was not significantly diminished with antiestrogen co-treatment. In addition, both sumithrin and fenvalerate were able to induce cell proliferation of MCF-7 cells in a dose-response fashion. Neither permethrin nor d-trans allethrin affected pS2 expression. Permethrin had a noticeable effect on cell proliferation at 100 microM, whereas d-trans allethrin slightly induced MCF-7 cell proliferation at 10 microM, but was toxic at higher concentrations. Overall, our studies imply that each pyrethroid compound is unique in its ability to influence several cellular pathways. These findings suggest that pyrethroids should be considered to be hormone disruptors, and their potential to affect endocrine function in humans and wildlife should be investigated.

Breast Neoplasms↗
PubMed1999

Predictors of plasma concentrations of DDE and PCBs in a group of U.S. women.

We evaluated predictors of plasma concentrations of dichlorodiphenyldichloroethylene (DDE), a metabolite of dichlorodiphenyltrichloroethane (DDT), and polychlorinated biphenyls (PCBs) in a group of 240 women, controls from a breast cancer case-control study nested in the Nurses' Health Study. We considered personal attributes such as age, serum cholesterol, region of residence, adiposity, lactation, and dietary intake. DDE levels increased 0.17 ppb/year of age (p = 0.0003), and PCBs increased 0.08 ppb (p = 0.0001). DDE and PCBs increased 0.20 (p = 0.02) and 0.13 ppb (p = 0.001), respectively, per 10 mg/dl serum cholesterol. Women living in the western United States had higher levels of DDE (mean = 11.0 ppb; p = 0.003), and women in the Northeast and Midwest had higher levels of PCBs (mean = 5.6 ppb; p = 0.0002) as compared to women from other parts of the country (mean DDE = 6.3; mean PCBs = 4. 5 ppb). Levels of DDE could not be predicted from consumption of meat, fish, poultry, dairy products, vegetables, fruits, and grains. There was a positive association between fish consumption and PCB concentrations among women in the Northeast and Midwest. Using data from the cases in the nested case-control study to assess the predictive ability of the models, we confirmed that the most reliable predictors of DDE were age and serum cholesterol, and the most important predictors of PCBs were age, serum cholesterol, and residence in the Midwest or Northeast. The null results for the majority of the food variables suggest that specific dietary factors, other than fish, are not currently a substantial contributor to human exposure to DDE and PCBs.

Adult↗
PubMed1999

Pesticides and inner-city children: exposures, risks, and prevention.

Six million children live in poverty in America's inner cities. These children are at high risk of exposure to pesticides that are used extensively in urban schools, homes, and day-care centers for control of roaches, rats, and other vermin. The organophosphate insecticide chlorpyrifos and certain pyrethroids are the registered pesticides most heavily applied in cities. Illegal street pesticides are also in use, including tres pasitos (a carbamate), tiza china, and methyl parathion. In New York State in 1997, the heaviest use of pesticides in all counties statewide was in the urban boroughs of Manhattan and Brooklyn. Children are highly vulnerable to pesticides. Because of their play close to the ground, their hand-to-mouth behavior, and their unique dietary patterns, children absorb more pesticides from their environment than adults. The long persistence of semivolatile pesticides such as chlorpyrifos on rugs, furniture, stuffed toys, and other absorbent surfaces within closed apartments further enhances urban children's exposures. Compounding these risks of heavy exposures are children's decreased ability to detoxify and excrete pesticides and the rapid growth, development, and differentiation of their vital organ systems. These developmental immaturities create early windows of great vulnerability. Recent experimental data suggest, for example, that chlorpyrifos may be a developmental neurotoxicant and that exposure in utero may cause biochemical and functional aberrations in fetal neurons as well as deficits in the number of neurons. Certain pyrethroids exert hormonal activity that may alter early neurologic and reproductive development. Assays currently used for assessment of the toxicity of pesticides are insensitive and cannot accurately predict effects to children exposed in utero or in early postnatal life. Protection of American children, and particularly of inner-city children, against the developmental hazards of pesticides requires a comprehensive strategy that monitors patterns of pesticide use on a continuing basis, assesses children's actual exposures to pesticides, uses state-of-the-art developmental toxicity testing, and establishes societal targets for reduction of pesticide use.

Adult↗
PubMed1999

Clinical evaluation of the effect of a remineralizing toothpaste on dentinal sensitivity.

Dentinal hypersensitivity is a common dental problem without a satisfactory solution. Most therapies have focused on either trying to block the stimulation of dentinal nerves or on sealing open dentinal tubules. This study evaluated, in a double blind clinical trial, the effect of Enamelon, a dentifrice containing sodium fluoride, calcium salts and phosphate salts (calcium separated from the phosphate and fluoride by a plastic divider in the tube to prevent interaction) on dentinal hypersensitivity over an 8-week period. A conventional OTC dentifrice containing NaF without calcium and phosphate enhancement served as the control. A third dentifrice, containing sodium monofluorophosphate enhanced by calcium and phosphate salts, was also tested. Based upon subjective anecdotal information, net numbers of sensitive teeth which became non-sensitive, and a logit analysis of the change in the proportion of sensitive teeth over the study time period, Enamelon was the most effective product, and the OTC control the least effective.

Analysis of Variance↗
PubMed1998

Estrogenic and antiprogestagenic activities of pyrethroid insecticides.

Many pesticides possess hormonal activity and have thus been classified as endocrine disruptors. Pyrethroids are commonly used insecticides worldwide, but little has been done to characterize their hormone agonist/antagonist potential. We tested four frequently encountered pyrethroids, fenvalerate, sumithrin, d-trans allethrin, and permethrin, for estrogen and progesterone agonist/antagonist activities using the Ishikawa Var-I human endometrial cancer cell line and the T47D human breast cancer cell line. Both cell lines produce alkaline phosphatase as an indicator of hormonal activity. Fenvalerate and sumithrin demonstrated significant estrogenicity; at concentrations of 10 microM, these compounds achieved maximal activities comparable to that of 10 nM 17alpha-ethynylestradiol in Ishikawa Var-I cells. None of the four compounds showed statistically significant estrogen antagonist activity or acted as progestins. However, fenvalerate and d-trans allethrin significantly antagonized the action of progesterone in T47D cells. Through these hormonal pathways, exposure to certain pyrethroids may contribute to reproductive dysfunction, developmental impairment, and cancer.

Alkaline Phosphatase↗
PubMed1998

CYP17 genotype and breast cancer risk.

The MspAI polymorphism in the 5' untranslated region of CYP17 has been evaluated as a breast cancer risk factor in a hospital-based case-control study in New York City. The study population consisted of 363 women [123 breast cancer patients and 240 patient controls (123 benign breast disease without atypical hyperplasia, 117 women without breast disease)]. There were 224 Caucasians (76 cases, 148 controls), 55 African-Americans (20 cases, 35 controls) and 84 Hispanics (27 cases, 57 controls); 142 premenopausal women and 221 postmenopausal women. Consistent with a previous report (Feigelson et al., Cancer Res., 57: 1063-1065, 1997) we found no evidence to implicate the minor variant (restriction site present allele, designated A2) as a breast cancer risk factor. Furthermore, we sought evidence to implicate the minor variant of CYP17 in the development of more aggressive breast cancers (n = 38/121) as had been reported previously. Although confidence intervals (CI) overlap, the data presented here do not provide support for previously reported findings (odds ratio, 0.9; 95% CI, 0.4-2.0; n = 38 versus odds ratio, 2.5; 95% CI, 1.1-5.2; n = 40). Clearly this question needs to be resolved in a larger study. No evidence was found to support the contention that inheritance of the minor variant is a predictor of early age at menarche. Allelic frequencies between different ethnic groups were not found to be different with the exception of Hispanic controls, in which the genotypic distribution was not consistent with the Hardy-Weinberg equilibrium.

Black People↗
PubMed1997

Plasma organochlorine levels and the risk of breast cancer.

BACKGROUND: Exposure to "environmental estrogens" such as organochlorines in pesticides and industrial chemicals has been proposed as a cause of increasing rates of breast cancer. Several studies have reported higher blood levels of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE) and polychlorinated biphenyls (PCBs) in patients with breast cancer than in controls. METHODS: We measured plasma levels of DDE and PCBs prospectively among 240 women who gave a blood sample in 1989 or 1990 and who were subsequently given a diagnosis of breast cancer before June 1, 1992. We compared these levels with those measured in matched control women in whom breast cancer did not develop. Data on DDE were available for 236 pairs, and data on PCBs were available for 230 pairs. RESULTS: The median level of DDE was lower among case patients than among controls (4.71 vs. 5.35 parts per billion, P=0.14), as was the median level of PCBs (4.49 vs. 4.68 parts per billion, P=0.72). The multivariate relative risk of breast cancer for women in the highest quintile of exposure as compared with women in the lowest quintile was 0.72 for DDE (95 percent confidence interval, 0.37 to 1.40) and 0.66 for PCBs (95 percent confidence interval, 0.32 to 1.37). Exposure to high levels of both DDE and PCBs was associated with a nonsignificantly lower risk of breast cancer (relative risk for women in the highest quintiles of both DDE and PCBs as compared with women in the lowest, 0.43; 95 percent confidence interval, 0.13 to 1.44). CONCLUSIONS: Our data do not support the hypothesis that exposure to DDT and PCBs increases the risk of breast cancer.

Adult↗
PubMed1997

A murine model of genetic susceptibility to lead bioaccumulation.

Previous reports have shown that blood lead levels in humans are associated with a polymorphic form of delta-aminolevulinate dehydratase (ALAD), an enzyme of heme biosynthesis that binds and is inhibited by lead. We hypothesized that ALAD levels may influence the distribution and accumulation of lead in the blood and target organs. To assess this, we studied strains of mice that differ in the numbers of copies of the ALAD gene. Our findings showed that mice with a duplication of the ALAD gene (DBA) accumulated twice the amount of lead in their blood and had higher lead levels in kidney and liver than mice with a single copy of the gene (C57) exposed to the same oral doses of lead during adulthood. Hybrid animals showed intermediate blood lead levels. Levels of blood zinc protoporphyrin (ZPP) increased with lead exposure in C57 animals while they were not affected in DBA mice, suggesting protection from production of this abnormal enzyme in mice with a duplication of the gene. Except for these protective effects in the formation of ZPP in DBA animals, duplication of the ALAD gene was found to increase lead accumulation. We conclude that although these mouse strains do not precisely replicate the polymorphism observed in humans, they may be used as a model to study genetic influences in lead bioaccumulation. Understanding genetic factors that affect susceptibility to lead-induced intoxication could have important implications for public health and intervention initiatives. These mouse strains may represent a useful model for future study of the role of ALAD in lead intoxication.

Administration, Oral↗
PubMed1997

Blood levels of DDT and breast cancer risk among women living in the north of Vietnam.

A positive association has been reported between elevated tissue organochlorines (p,p'-DDT/p,p'-DDE, PCBs, dioxins) and breast cancer in some case-control studies and occupational cohort studies. We previously reported high serum levels of p,p'-DDT and its metabolite p,p'-DDE in women living throughout Vietnam. We report here the results of a small hospital-based case-control study examining the association between blood levels of p,p'-DDT/p,p'-DDE and the risk of invasive breast cancer among residents of the north of Vietnam-an area where insecticides such as p,p'-DDT have been heavily used in the recent past. The study was conducted among patients admitted to a single hospital in the capital city of Hanoi in 1994. Study subjects were 21 women newly diagnosed with invasive adenocarcinoma of the breast, who served as cases, and 21 women of similar age with fibrocystic breast disease, who served as controls. No increase was evident in the relative risk of breast cancer with increasing tertiles of serum concentration of the compounds of interest, even after adjustment for major potential confounders, such as age at menarche, parity, history of lactation, and body weight. These results suggest that recent and past exposure to p,p'-DDT does not play an important role in the etiology of breast cancer among women living in a country with a tropical climate where insecticide use for mosquito control is common.

Adult↗
PubMed1997

Breast cancer risk and environmental exposures.

Although environmental contaminants have potential to affect breast cancer risk, explicit environmental links to this disease are limited. The most well-defined environmental risk factors are radiation exposure and alcohol ingestion. Diet is clearly related to the increased incidence of breast cancer in developed countries, but its precise role is not yet established. Recent studies have implicated exposure to organochlorines including DDT as a risk factor for breast cancer in the United States, Finland, Mexico, and Canada. Other investigations have discovered associations between breast cancer risk and exposures to chemical emissions and some occupational exposures. Several points must be considered in evaluating the relationship of environmental exposure to breast cancer. Among these considerations are the mechanism of tumorigenesis, timing of environmental exposure, and genetic modulation of exposure. Epidemiologic and ecologic investigations must take into account the very complex etiology of breast cancer and the knowledge that tumorigenesis can arise from different mechanisms. Thus crucial exposures as well as reproductive events related to breast cancer may occur years before a tumor is evident. Moreover, environmental contaminants may alter reproductive development, directly or indirectly, and thereby effect the course of tumorigenesis. Such alterations include change in gender, change in onset of puberty, and inhibition or promotion of tumor formation. Timing of exposure is therefore important with respect to mechanism and susceptibility. Finally, genetic polymorphisms exist in genes that govern capacity to metabolize environmental contaminants. Higher risk may occur among persons whose enzymes either are more active in the production of procarcinogens or fail to detoxify carcinogenic intermediates formed from chemicals in the environment.

Breast Neoplasms↗
PubMed1997

p53 haplotype determination in breast cancer.

Inheritance of certain germ line haplotypes consisting of three biallelic polymorphisms of p53 has been proposed as a risk factor for breast cancer and colorectal cancer [A. Själander et al., Carcinogenesis (Lond.), 17: 1313-1316, 1996, and Carcinogenesis (Lond.), 16: 1461-1464, 1995]. In their studies, pairwise haplotypes of these three polymorphisms were estimated. Extended haplotypes were further projected from the pairwise combinations. To overcome the necessity to estimate pairwise and extended haplotype frequencies, a PCR method has been developed to determine the absolute extended p53 haplotypes in diploid genomes. The method requires allele-specific PCR, confirmed by restriction analysis, and successive amplicon analysis. It has been applied to a nested case-control study of breast cancer (284 subjects; 99 cases and 185 controls; 182 Caucasians, 56 Hispanics, and 46 African-Americans). Evidence is presented that minor variants of the intron 3, codon 72, and intron 6 polymorphisms were moderately elevated in Caucasian breast cancer cases (intron 3, P = 0.03 for genotype and P = 0.01 for allelic frequency; codon 72, P = 0.07 for genotype and P = 0.054 for allelic frequency; and intron 6, P = 0.02 for genotype and P = 0.02 for allele frequency). Accordingly, analysis of haplotype distributions suggested an association of minor p53 haplotypes with breast cancer risk in Caucasians (P = 0.07). The relative allelic frequencies in breast cancer cases compared with controls also differed by age and menopausal status; the 1-2-1 haplotype was overrepresented in postmenopausal cases (P = 0.02) and cases older than 50 years (P = 0.02), whereas the other minor haplotypes (1-1-2 and rare variants) were overrepresented in premenopausal cases (P = 0.003) and cases 50 years of age and younger (P = 0.02). Genotype distributions at each locus and for all control groups were consistent with Hardy-Weinberg equilibria. Differences in haplotype distribution were associated with ethnicity (Caucasians versus African-Americans and Caucasians versus Hispanics, P < 0.001). The new haplotyping method may be useful in the study of gene-environment interactions.

Adult↗
PubMed1997

Temporal variation in chlorinated hydrocarbons in healthy women.

Chlorinated hydrocarbons may increase breast cancer risk. Most epidemiological studies addressing this possibility have used one biological sample to measure a subject's cumulative exposure to these compounds. Little is known about short-term temporal variation in organochlorines, particularly in individuals with low levels. Thus, the reliability of using one sample to assess blood levels of chlorinated hydrocarbons in an epidemiological study is unknown. To better understand the temporal changes in blood measures among women with nonoccupational exposures to these compounds, we collected two 5-ml blood samples, an average of 2 months apart, from each of 31 nonfasting healthy women, ages 45-81 years. Samples were assayed for 1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene (DDE), polychlorinated biphenyls (PCBs), and trans-nonachlor in blinded, matched pairs. Results were adjusted for estimated total plasma lipids. The correlations between the two blood samples were high for DDE and PCBs (lipid-adjusted, r = 0.96 and r = 0.89, respectively). For trans-nonachlor, the correlation was relatively poor (lipid-adjusted r = 0.57); however, with the removal of one outlier, the correlation improved substantially (lipid-adjusted, r = 0.90). The mean difference between the two blood samples in unadjusted [-0.36 ng/ml, 95% confidence interval (CI), -0.97, 0.24 ng/ml, P = 0.23] and lipid-adjusted (-0.035 microgram/g lipid; 95% CI, -0.124, 0.055; P = 0.44) DDE levels was small. Similarly, there was little change in the mean difference for unadjusted (-0.14 ng/ml; 95% CI, -0.53, 0.25 ng/ml; P = 0.47) and lipid-adjusted (0.006 microgram/g lipid; 95% CI, -0.050, 0.062; P = 0.82) PCB levels. The mean differences in trans-nonachlor levels between the two blood draws were also small: unadjusted (-0.03 ng/ml; 95% CI, -0.07, 0.02 ng/ml; P = 0.20) and lipid-adjusted (-0.003 microgram/g lipid; 95% CI, -0.010, 0.004; P = 0.33). These data suggest that temporal changes in organochlorine levels within a 1 to 3-month period are minimal for noncancer patients and that a single measure for estimating exposure is highly reliable for DDE and PCB. For trans-nonachlor, however, where the correlation between blood draws was lower, three samples would be needed for estimating exposure; if an outlier is removed from our data, however, then we can conclude that only a single measure is sufficient. These data, therefore, offer no clear conclusion for the use of a single measurement for trans-nonachlor.

Aged↗