The use of a tape recorder in clinical practice.
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Humans↗
Biomedical subjects
A Weston
Publications and source records attributed to A Weston.
Genotoxicity of chemical and physical agents in cultured human tissues and cells.
In vitro model systems have recently been developed to investigate the toxicity of chemical, microbial and physical agents in normal human tissues and cells from many of the major tissue sites of high cancer incidence. Pathobiological endpoints used in these studies include alterations in incorporation rates of precursors into DNA, RNA and protein, in the clonal growth rate of cultured cells and in DNA structure (e.g. single-strand breaks, DNA-protein crosslinks and chemical-DNA adducts) and the induction of differentiation, chromosomal and karyotypic abnormalities, mutations and neoplastic transformation. These systems have been used to study a variety of complex mixtures and individual substances, including cigarette smoke components such as benzo[a]pyrene and N-nitrosamines, formaldehyde, fecapentaenes, asbestos, and nickel and chromium ions. In addition, increasing awareness of the role of oncogenes in human carcinogenesis has led to studies involving transfection experiments with oncogenes and hepatitis B viral genes in normal human cells.
Asbestos↗
Derivative fluorescence spectral analysis of polycyclic aromatic hydrocarbon-DNA adducts in human placenta.
Metabolic activation in humans of chemical carcinogens found in the environment results in the formation of carcinogen-DNA adducts in vivo. Some polycyclic aromatic hydrocarbon-DNA adducts in human DNA can be hydrolyzed under mildly acidic conditions to yield tetrahydrotetrol derivatives which may then be detected by synchronous fluorescence spectroscopy. In an analysis of human placental DNA, second derivative spectroscopy alone was unable to resolve the synchronous fluorescent signature for r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene from a crude extract, because a complex array of other fluorescent materials was also present. Purification of the sample by a combination of chromatographic procedures including immunoaffinity chromatography and HPLC has now been shown to yield r-7,t-8,t-9,c-10-tetrahydroxy-7,8,9,10-tetrahydrobenzo[alpha]pyrene residues from human DNA that are spectroscopically pure at the second derivative level. Immunoaffinity columns were prepared with rabbit antiserum raised against DNA that had been modified with (+/-)-r-7,t-8-dihydroxy-t-9,10-epoxy-7,8,9,10-tetrahydrobenzo[alpha]pyre ne. This antiserum has now been shown to recognize DNA samples that have been modified with six different polycyclic aromatic hydrocarbon diol epoxides and is probably only specific for a broad spectrum of polycyclic aromatic hydrocarbon-DNA adducts. Adducts were eluted from the immunoaffinity columns, hydrolyzed with acid, and extracted into isoamyl alcohol, before being subjected to high-performance liquid chromatography. These experiments reveal important limitations of second derivative fluorescence spectroscopy as a tool in the analysis of complex environmental mixtures. Furthermore, they extensively define the ability of anti-benzo[alpha]pyrenediol epoxide-DNA antibodies to recognize different types of polycyclic aromatic hydrocarbon-DNA adducts.
Biotransformation↗
Allelic frequency of a p53 polymorphism in human lung cancer.
p53 is a tumor suppressor gene that is mutated in diverse tumor types. Here we report the frequencies of common polymorphic variants at codon 72 of the p53 gene in germline DNA of lung cancer cases and controls as determined by a polymerase chain reaction strategy. The observed allelic distribution was found to be significantly different between African-Americans and Caucasians in this U.S. population. The frequency of polymorphic variants was similar in lung cancer cases and controls after adjustment for race. However, among lung cancer patients the proline variant at codon 72 was in excess in adenocarcinoma patients by comparison with other histologies.
Adenocarcinoma↗
Host factors in lung cancer risk: a review of interdisciplinary studies.
Host-specific factors influence risk for lung cancer. A few case-control and family studies of lung cancer susceptibility allowed for known lung cancer carcinogens and showed strong familial clustering with some evidence for a codominantly acting major gene. Cytochrome P-450 enzymes (e.g., CYP1A1) activate many carcinogens in tobacco smoke but have shown inconsistent associations with risk for lung cancer. Case-control studies that assess the effects of CYPIID6 on lung cancer risk have consistently shown a mildly decreased risk for lung cancer among poor metabolizers. Cell surface markers have shown little relation to risk for lung cancer. Studies involving DNA or hemoglobin adducts, sister chromatid exchange, or oncogene activation only indirectly measure host-specific risk, and these assays have suffered from poor reproducibility and high cost. We describe epidemiological designs to assess specific genetic factors that may alter lung cancer risk.
Biomarkers↗
Lung cancer, race, and a CYP1A1 genetic polymorphism.
The assessment of human cancer risk using molecular epidemiological techniques involves determining the relative contributions of inherited and acquired genetic predispositions, in the context of environmental exposures. Recently described genetic polymorphisms for CYP1A1, a gene involved in the metabolic activation of polycyclic aromatic hydrocarbons, have been associated with lung cancer risk in a Japanese population. We report herein findings from a United States case-control study of lung cancer (56 cases; 48 controls). The polymerase chain reaction followed by an Msp1 restriction enzyme digestion was used to analyze constitutive DNA but no association between the restriction fragment length polymorphism and lung cancer risk was found (odds ratio, 0.7; 95% confidence interval, = 0.3-1.6). Analysis of genotype by cumulative smoking status did not reveal an elevated risk among lesser or greater smokers. The presence of the CYP1A1 Msp1 site-present allele, which was previously found to be associated with Japanese lung cancer risk, was statistically increased in African compared to Caucasian Americans (odds ratio, 2.9; 95% confidence interval, 1.2-2.7). When stratified by race, however, no association between case status and the polymorphism was observed, but the small number of study subjects within each racial group limited the statistical power. Larger studies are required to evaluate the risk of the CYP1A1 Msp1 polymorphism in African Americans.
Asthma↗