Associations between Polycyclic Aromatic Hydrocarbon–Related Exposures and p53 Mutations in Breast Tumors

Background: Previous studies have suggested that polycyclic aromatic hydrocarbons (PAHs) may be associated with breast cancer. However, the carcinogenicity of PAHs on the human breast remains unclear. Certain carcinogens may be associated with specific mutation patterns in the p53 tumor suppressor gene, thereby contributing information about disease etiology. Objectives: We hypothesized that associations of PAH-related exposures with breast cancer would differ according to tumor p53 mutation status, effect, type, and number. Methods: We examined this possibility in a population-based case–control study using polytomous logistic regression. As previously reported, 151 p53 mutations among 859 tumors were identified using Surveyor nuclease and confirmed by sequencing. Results: We found that participants with p53 mutations were less likely to be exposed to PAHs (assessed by smoking status in 859 cases and 1,556 controls, grilled/smoked meat intake in 822 cases and 1,475 controls, and PAH–DNA adducts in peripheral mononuclear cells in 487 cases and 941 controls) than participants without p53 mutations. For example, active and passive smoking was associated with p53 mutation–negative [odds ratio (OR) = 1.55; 95% confidence interval (CI), 1.11–2.15] but not p53 mutation–positive (OR = 0.77; 95% CI, 0.43–1.38) cancer (ratio of the ORs = 0.50, p < 0.05). However, frameshift mutations, mutation number, G:C→A:T transitions at CpG sites, and insertions/deletions were consistently elevated among exposed subjects. Conclusions: These findings suggest that PAHs may be associated with specific breast tumor p53 mutation subgroups rather than with overall p53 mutations and may also be related to breast cancer through mechanisms other than p53 mutation

Calcium ion currents mediating oocyte maturation events

During maturation, the last phase of oogenesis, the oocyte undergoes several changes which prepare it to be ovulated and fertilized. Immature oocytes are arrested in the first meiotic process prophase, that is morphologically identified by a germinal vesicle. The removal of the first meiotic block marks the initiation of maturation. Although a large number of molecules are involved in complex sequences of events, there is evidence that a calcium increase plays a pivotal role in meiosis re-initiation. It is well established that, during this process, calcium is released from the intracellular stores, whereas less is known on the role of external calcium entering the cell through the plasma membrane ion channels. This review is focused on the functional role of calcium currents during oocyte maturation in all the species, from invertebrates to mammals. The emerging role of specific L-type calcium channels will be discussed

Corrosion Performance of Friction Stir Linear Lap Welded AM60B Joints

A corrosion investigation of friction stir linear lap welded AM60B joints used to fabricate an Mg alloy-intensive automotive front end sub-assembly was performed. The stir zone exhibited a slightly refined grain size and significant break-up and re-distribution of the divorced Mg17Al12 (β-phase) relative to the base material. Exposures in NaCl (aq) environments revealed that the stir zone was more susceptible to localized corrosion than the base material. Scanning vibrating electrode technique measurements revealed differential galvanic activity across the joint. Anodic activity was confined to the stir zone surface and involved initiation and lateral propagation of localized filaments. Cathodic activity was initially confined to the base material surface, but was rapidly modified to include the cathodically-activated corrosion products in the filament wake. Site-specific surface analyses revealed that the corrosion observed across the welded joint was likely linked to variations in Al distribution across the surface film/metal interface

Development of antibody-based fiber-optic sensors for detection of a benzo[a]pyrene metabolite.

This paper describes the development of an antibody-based fiber-optic sensor designed to detect benzo[a]pyrene (BP) metabolites, in this case r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (benzopyrenetetraol or BPT), a naturally fluorescent hydrolysis product of DNA adducts that forms during BP metabolism. The sensor's principle of operation is based on diffusion of BPT Into the fiber's reagent phase where it complexes with monoclonal antl-BPT antibody. Reagent phase is immobilized Inside a reusable sensing tip. It consists of either membrane-entrapped liquid antibody or antibody Immobilized on 7-μm silica beads. The antibody binds and concentrates BPT in the fiber's viewing region until equilibrium with the sample is achieved. Typical measurements are performed in 15 min under nonequilibrium conditions. The 325-nm line of a He:Cd laser provides excitation of the immune complex. The Intensity of the resulting fluorescence emission is directly proportional to the amount of BPT in the sample. Sensor response rate varies with BPT concentration in the sample and, under certain circumstances, with antibody concentration in the sensor. At high antibody concentrations, sensor response rate is linear for about 2 h. For 15-min incubations, typical limits of detection are 5 X 10-10M. Significant chemical selectivity is also demonstrated despite the presence of structurally and spectrally similar polynuclear aromatic (PNA) interferents. These results indicate that the fluorolmmunosensor (FIS) is capable of performing highly sensitive and selective immunoassays and could be useful as a screening instrument for BP metabolites in biological samples. Furthermore, the Information provided by this work should be generally applicable to the development of devices for chemically similar systems. © 1988, American Chemical Society. All rights reserved

Development of antibody-based fiber-optic sensors for detection of a benzo[a]pyrene metabolite.

This paper describes the development of an antibody-based fiber-optic sensor designed to detect benzo[a]pyrene (BP) metabolites, in this case r-7,t-8,9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[a]pyrene (benzopyrenetetraol or BPT), a naturally fluorescent hydrolysis product of DNA adducts that forms during BP metabolism. The sensor's principle of operation is based on diffusion of BPT Into the fiber's reagent phase where it complexes with monoclonal antl-BPT antibody. Reagent phase is immobilized Inside a reusable sensing tip. It consists of either membrane-entrapped liquid antibody or antibody Immobilized on 7-μm silica beads. The antibody binds and concentrates BPT in the fiber's viewing region until equilibrium with the sample is achieved. Typical measurements are performed in 15 min under nonequilibrium conditions. The 325-nm line of a He:Cd laser provides excitation of the immune complex. The Intensity of the resulting fluorescence emission is directly proportional to the amount of BPT in the sample. Sensor response rate varies with BPT concentration in the sample and, under certain circumstances, with antibody concentration in the sensor. At high antibody concentrations, sensor response rate is linear for about 2 h. For 15-min incubations, typical limits of detection are 5 X 10-10M. Significant chemical selectivity is also demonstrated despite the presence of structurally and spectrally similar polynuclear aromatic (PNA) interferents. These results indicate that the fluorolmmunosensor (FIS) is capable of performing highly sensitive and selective immunoassays and could be useful as a screening instrument for BP metabolites in biological samples. Furthermore, the Information provided by this work should be generally applicable to the development of devices for chemically similar systems. © 1988, American Chemical Society. All rights reserved

Dependence of cancer risk from environmental exposures on underlying genetic susceptibility: an illustration with polycyclic aromatic hydrocarbons and breast cancer

BACKGROUND: Most studies of environmental risk factors and breast cancer are conducted using average risk cohorts. METHODS: We examined the association between polycyclic aromatic hydrocarbon (PAH)-albumin adducts in bloods from baseline and breast cancer risk in a prospective nested case-control study (New York site of the BCFR, 80 cases and 156 controls). We estimated the 10-year absolute breast cancer risk by a risk model that uses pedigree information (BOADICEA) and evaluated whether the increased risk from PAH differed by absolute risk. RESULTS: Women with detectable levels of PAH had a twofold association with breast cancer risk (odds ratio (OR)=2.04; 95% CI=1.06-3.93) relative to women with non-detectable levels. The association increased with higher levels of PAH (⩾median) and by a higher level of absolute breast cancer risk (10-year risk ⩾3.4%: OR=4.09, 95% CI=1.38-12.13). CONCLUSIONS: These results support that family-based cohorts can be an efficient way to examine gene-environment interactions