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Biomedical subjects

C C Harris

Publications and source records attributed to C C Harris.

At least 325 records · Page 18Linked to original sources
PubMed1985

Effects of formaldehyde, acetaldehyde, benzoyl peroxide, and hydrogen peroxide on cultured normal human bronchial epithelial cells.

The effects of several aldehydes and peroxides on growth and differentiation of normal human bronchial epithelial cells were studied. Cells were exposed to formaldehyde, acetaldehyde, benzoyl peroxide (BPO), or hydrogen peroxide (HPO). The effect of each agent on the following parameters was measured: (a) clonal growth rate; (b) squamous differentiation; (c) DNA damage; (d) ornithine decarboxylase activity; (e) nucleic acid synthesis; (f) aryl hydrocarbon hydroxylase activity; and (g) arachidonic acid and choline release. None of the agents were mitogenic, and their effects were assessed at concentrations which reduced growth rate (population doublings per day) to 50% of control. The 50% of control concentrations for the 6-h exposure were found to be 0.065 mM BPO, 0.21 mM formaldehyde, 1.2 mM HPO, and 30 mM acetaldehyde. BPO-exposed cells were smaller than controls (median cell planar area, 620 sq microns versus 1150 sq microns), and acetaldehyde-exposed cells were larger than controls (median cell planar area, 3200 sq microns). All agents increased the formation of cross-linked envelopes and depressed RNA synthesis more than DNA synthesis. HPO caused DNA single-strand breaks, while formaldehyde and BPO caused detectable amounts of both single-strand breaks and DNA-protein cross-links. Other effects included increased arachidonic acid and choline release due to HPO. The similarities and differences of the effects of these aldehydes and peroxides to those caused by tumor promoters are discussed.

Acetaldehyde↗
PubMed1985

Rat and human explant metabolism, binding studies, and DNA adduct analysis of benzo(a)pyrene and its 6-nitro derivative.

Human colon and bronchus tissue explants were incubated with either [3H]benzo(a)pyrene ([3H]BP) or [3H]-6-nitrobenzo(a)pyrene ([3H]-6-NBP). The total percentage of metabolism of BP and 6-NBP was, respectively, 8-59% and 18-41% in bronchus and 11-23% and 36-50% in colon. A product tentatively identified as 3-hydroxy-6-NBP was isolated from the 6-NBP incubation medium. BP and 6-NBP when incubated at equivalent concentrations were found to bind covalently to the DNA of human bronchi from 15 cases at means of 42 and 50.9 pmol/10 mg DNA, respectively, and to the DNA of human colon from 6 cases at means of 66.5 and 35 pmol/10 mg DNA, respectively. The range among individuals was within one order of magnitude. High pressure liquid chromatography (HPLC) of enzymic hydrolysates of human bronchus explant DNA revealed one adduct from the BP-incubated bronchus which cochromatographed with (+/-)-7,8-dihydroxy-9,10-epoxy-7,8,9, 10-tetrahydrobenzo(a)pyrene-deoxyguanosine and a possible two adducts from the 6-NBP-incubated bronchus which eluted earlier than did the BP adduct. DNA obtained from the lung or liver of rats given 2.0-mg/kg doses of either [3H]BP or [3H]-6-NBP by i.p. injection was also enzymically hydrolyzed and analyzed on HPLC. Three DNA adducts were observed in liver and two were observed in lung DNA hydrolysates from rats given injections of [3H]BP. One adduct from each organ cochromatographed with (+/-)-7,8-dihydroxy-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene- deoxyguanosine; however, the major adduct in each case eluted earlier. Only one adduct was detected in liver and lung DNA hydrolysates from rats given [3H]-6-NBP, and this had the same retention time as did the major adduct isolated from human bronchus that had been incubated previously with [3H]-6-NBP. Salmonella typhimurium TA98 was incubated with [3H]-6-NBP and Aroclor-induced rat liver S9. Enzymically hydrolyzed DNA analyzed by HPLC revealed three adducts, two of which cochromatographed with the two DNA adducts isolated from human bronchus DNA adduct which had the same retention time as did the major liver and lung DNA adduct from rats given i.p. injections of [3H]-6-NBP. In each case the major adduct from DNA hydrolysates of rat liver and lung, human bronchus, and S. typhimurium, all treated with [3H]-6-NBP, cochromatographed with the major DNA adduct isolated from liver and lung DNA of rats given [3H]BP.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1984

Effects of aplysiatoxin and debromoaplysiatoxin on growth and differentiation of normal human bronchial epithelial cells.

The effects of aplysiatoxin and debromoaplysiatoxin on the clonal growth rate, cross-linked envelope formation and plasminogen activator secretion of normal human bronchial epithelial cells were studied. Neither compound was mitogenic over a wide range of concentrations (10(-13) to 10(-7)M). Both aplysiatoxin and debromoaplysiatoxin inhibited clonal growth rate with 50% inhibitory concentrations of 3 x 10(-11)M and 10(-10)M, respectively. Both compounds induced the formation of cross-linked envelopes and increased plasminogen activator secretion with equal potency. These data are similar to those previously obtained with 12-O-tetradecanoylphorbol-13-acetate and teleocidin B and suggest that aplysiatoxin and debromoaplysiatoxin induce terminal squamous differentiation in normal human bronchial epithelial cells.

Bronchi↗
PubMed1984

Activation of chemical carcinogens by cultured human fetal liver, esophagus and stomach.

Cultured fetal human stomach, esophagus and liver activated benzo[a]pyrene (BP), aflatoxin B1 (AFB) and certain N-nitrosamines into metabolites that bound to cellular DNA. When the 3 organs were compared the highest level of activity was observed in the stomach. The interindividual variation was 10-fold and the amount of carcinogen-DNA adducts did not correlate with the sex or age of the fetus. The reaction products between BP or AFB and cellular DNA were investigated in liver explants. The carcinogen-DNA adduct patterns were identical to those observed in adult human tissues; BPDEI-Gua being the major adduct formed by BP and 2,3-dihydro-2-(7'-guanyl)-3-hydroxy-AFB by AFB. The results indicate that fetal organs can metabolize those oncogenic compounds at an early stage of the development, and that the metabolic pathways and DNA adducts are quite similar to those in experimental animals in which the compounds are carcinogenic.

Aflatoxin B1↗
PubMed1984

Bombesin and the C-terminal tetradecapeptide of gastrin-releasing peptide are growth factors for normal human bronchial epithelial cells.

Bombesin and the C-terminal portion of gastrin-releasing peptide (GRP14-27) each increase clonal growth rate and colony-forming efficiency of normal human bronchial epithelial cells. These effects occur in the presence or absence of an optimal concentration (5 ng/ml) of epidermal growth factor (EGF). In contrast to EGF bombesin and GRP14-27 do not stimulate cell migration. Thus, bombesin and the C-terminal fragment of gastrin-releasing peptide represent a new class of peptides mitogenic for normal human epithelial cells.

Adult↗
PubMed1984

Energy and spatial distribution of multiple order Compton scatter in SPECT: a Monte Carlo investigation.

Energy and spatial projection distributions were simulated for gamma camera imaging of multiple order Compton scattered photons. SPECT imaging of a line source of radioactivity located in a water filled cylindrical phantom was modelled using Monte Carlo techniques. Photon trajectories were followed from emission to detection including the effects of all physical interactions and the resulting energy spectra and spatial projections were sorted as a function of the number of times the photon underwent Compton scattering before detection. Analysis of energy spectra demonstrates that Compton events up to second order overlap with the non-scattered events and distributions are peaked at lower energies as the scattering order increases. Analysis of spatial projections shows that, with increasing order, Compton events produce tails on the line spread function which progress from roughly exponential to nearly flat distributions. The use of Monte Carlo modelling thus allows a detailed investigation of the spatial and energy distribution of Compton scatter which could not be performed using present experimental techniques.

Models, Theoretical↗
PubMed1984

Acute effects of 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, or 2,3,7,8-tetrachlorodibenzo-p-dioxin on cultured normal human bronchial epithelial cells.

Effects of teleocidin B, 12-O-tetradecanoylphorbol-13-acetate (TPA), phorbol, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 2,7-dichlorodibenzo-p-dioxin (DCDD) on normal human bronchial epithelial cell cultures were assessed by quantitation of cellular morphology, clonal growth (population doublings per day), cross-linked envelope (CLE) formation and the enzymatic activities of aryl hydrocarbon hydroxylase (AHH), ornithine decarboxylase (ODC) and plasminogen activator (PA). Toxicity was assessed by clonal growth assays. Teleocidin B and TPA had similar effects on growth, morphology and enzyme activities. When the cells were incubated with TPA or teleocidin B at concentrations of 1-100 nM for 6 h, RNA synthesis was unaffected, but DNA synthesis decreased and squamous differentiation, marked by an increase in cell surface area and cross-linked envelope formation, was increased. TPA and teleocidin B also increased ODC activity in LHC-0 medium (a maintenance medium without epidermal growth factor) but caused a decrease of ODC activity in LHC-4 (a growth medium containing epidermal growth factor). Finally, TPA and teleocidin B each caused an increase of PA and a decrease of AHH activities in both media. Phorbol, a non-promoting analogue of TPA, had no effect on growth, morphology or biochemical assays. TCDD (100 nM) caused a 15% decrease in cell growth when cells were incubated in LHC-4, and this was accompanied by an increase in cell surface area, PA activity, and CLE formation. TCDD caused an increase in AHH and ODC activities when the cells were incubated in either LHC-0 or LHC-4 medium. DCDD did not alter cell growth, and its morphological and biochemical effects were similar to those of TCDD although less marked. In conclusion, results reported here are consistent with the hypothesis that an important property of some tumor promoters is their ability to induce terminal differentiation in normal, non-initiated epithelial cells.

Alkaloids↗
PubMed1984

Ga-67 uptake in the lung in sarcoidosis.

Images were obtained with Ga-67 and bronchopulmonary lavage performed in 21 patients with sarcoidosis (31 studies). The Ga-67 index, a semiquantitative criterion, was compared to a quantitative computer index based on lung:liver activity ratios; accuracy in predicting active alveolitis (defined by lavage lymphocyte counts) was assessed and differences between 24- and 48-hour studies examined. Computer activity ratios correlated well with the Ga-67 index, which had a sensitivity of 64%, specificity of 71%, and accuracy of 68% compared to 71%, 82%, and 77%, respectively, for the computer scores. Scores at 24 and 48 hours were similar. These results suggest that (a) Ga-67 scanning is useful in staging activity in pulmonary sarcoidosis, (b) quantitative computer scores are accurate in predicting disease activity, and (c) scanning can be performed 24 or 48 hours after injection.

Adult↗
PubMed1984

Effect of region assignment on relative renal blood flow estimates using radionuclides.

To determine the value of the initial phase of the Tc-99m DTPA renogram in the direct estimation of relative renal blood flow in dogs, the ratios of the slopes of renal time-activity curves were compared with the ratios of measured blood flow. Radionuclide results were dependent on region-of-interest (ROI) and background ROI assignment, and correlated well with measured relative flow only with a maximum renal outline region. Curve slope ratios correlated well with measured flow ratios with and without background correction, while 1- to 2-minute uptake ratios correlated well only when corrected for background.

Animals↗
PubMed1984

Chemical carcinogenesis in the tracheobronchial epithelium.

Some of the recent work in pulmonary carcinogenesis is briefly reviewed. Morphologic studies of neoplastic and preneoplastic lesions of the human bronchi are compared with similar studies of carcinogenesis and epithelial regeneration in the hamster trachea. These studies suggest that bronchogenic carcinomas are typically complex mixtures of three basic phenotypes, the epidermoid and the mucous and dense-core granulated (endocrine) phenotypes. Pure forms of these phenotypes are rare, as different cells and even individual cells in single tumors express more than one phenotype. The clinical significance of such phenotypic variability is not yet known. Bronchial cell types which retain the capacity to divide include the mucous cell, the basal cell and perhaps the dense-core granulated cell. Studies of epithelial regeneration and preneoplastic lesions suggest that the mucous cell may be pivotal both in the response to injury and in carcinogenesis. Cigarette smoking is believed to be the major etiologic factor in bronchogenic carcinoma. Cigarette smoke contains initiators of carcinogenesis, but it contains a plethora of probable promoters and cocarcinogens as well. It is hypothesized that cigarette smoke may both initiate bronchial cells and promote carcinogenesis in cells which have previously been initiated by smoke or other factors. It is further hypothesized that that mucous cell is the major target for initiation and subsequent tumorigenesis. The ultimate phenotype(s) displayed by the tumor is suggested to result from the effect of microenvironmental factors upon the initiated cell and its progeny.

Animals↗
PubMed1984

Aberrant expression of keratin proteins and cross-linked envelopes in human esophageal carcinomas.

When compared to normal esophageal epithelium, marked alterations in keratin protein and cross-linked envelope expression were found in human esophageal carcinomas. Examination of the pattern of keratin proteins extracted from either several primary esophageal tumors or carcinomas xenotransplanted in nude mice revealed a dramatic reduction in the amount of keratin protein, especially in the Mr 52,000 to 61,000 range. In seven of eight of the primary tumors, the major Mr 52,000 and Mr 61,000 esophageal keratins were not detected, and the remaining tumor exhibited a marked reduction in these two keratins. The major Mr 57,000 and minor Mr 59,000 esophageal keratins were found in varying but reduced amounts in the different tumors. The major Mr 57,000 keratin seemed to be the most conserved keratin of this intermediate-molecular-weight keratin class (Mr 52,000 to 61,000). In contrast, the lower-molecular-weight keratins (Mr 46,000 to 50,500) were usually conserved in the carcinoma cells and were present at levels approximating that of the nontransformed counterpart. The minor Mr 37,000 and 44,000 keratins from normal esophageal epithelium were retained in the tumor cells but often in reduced amounts. The expression of another differentiated function, cross-linked envelopes, in the carcinoma cells varied from unimpaired to severely restricted capacity to form envelopes. In conclusion, specific alterations in keratin protein and cross-linked envelope expression were found in human esophageal carcinomas.

Animals↗
PubMed1984

Keratin proteins in human lung carcinomas. Combined use of morphology, keratin immunocytochemistry, and keratin immunoprecipitation.

Light-microscopic immunocytochemistry and electron microscopy demonstrated that adenocarcinomas (AC) and squamous cell (epidermoid) carcinomas (SCCs) of human lung contained keratin proteins in the form of tonofilament bundles. However, moderately differentiated (md) SCCs contained abundant keratin, whereas poorly differentiated (pd) SCCs and all ACs contained lesser amounts. Lung tumors with the diagnosis of AC or SCC, as defined by WHO criteria, were also analyzed by immunoprecipitation techniques for the presence of keratin proteins. Regardless of the degree of tumor differentiation, SCCs contained a 44 kd keratin which was lacking in ACs. Interestingly, normal bronchial epithelium also contained the same 44 kd keratin. In addition, as SCCs became more differentiated, they exhibited even greater differences in the profile of synthesized keratins. Specifically, the relative abundance of the intermediate-sized keratins (57 and 59 kd) was increased in the md SCCs. Although keratin protein patterns appear to be a valuable adjunct in distinguishing AC from SCC, their usefulness as a diagnostic tool will require survey of a larger number of poorly differentiated tumors.

Adenocarcinoma, Bronchiolo-Alveolar↗
PubMed1984

Repair of DNA damage caused by formaldehyde in human cells.

The alkaline elution technique was used to study repair of DNA damage caused by formaldehyde (HCHO) in human bronchial epithelial cells and fibroblasts, skin fibroblasts, and DNA excision repair-deficient skin fibroblasts from donors with xeroderma pigmentosum. Exposure of cells to HCHO resulted in DNA-protein cross-links (DPC) and DNA single-strand breaks (SSB) in all cell types. DPC were induced at similar levels and were also removed by all cell types, with a half removal time of 2 to 3 hr. HCHO caused more SSB in the normal cell types than in the xeroderma pigmentosum fibroblasts. However, in all cell types, including the xeroderma pigmentosum cells, HCHO-induced DNA SSB and DPC were removed at comparable rates. By excision repair of HCHO-induced DNA damage, normal cells generated SSB that were also readily repaired. HCHO was only moderately cytotoxic to normal bronchial epithelial cells and fibroblasts at concentrations that induced substantial DNA damage. HCHO enhanced the cytotoxicity of both ionizing radiation and N-methyl-N-nitrosourea in both cell types. The results indicate that most DPC caused by HCHO can be removed without the involvement of DNA excision repair. Furthermore, HCHO also directly causes DNA SSB as well as SSB generated indirectly during ultraviolet-type excision repair. These studies indicate the complexity of the HCHO-induced DNA damage and its repair and that HCHO may enhance the cytotoxicity of chemical and physical carcinogens in human cells.

Animals↗
PubMed1984

Differential effects of 12-O-tetradecanoylphorbol-13-acetate on cultured normal and neoplastic human bronchial epithelial cells.

The effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) on 10 human lung carcinoma cell lines were compared to those seen on normal human bronchial epithelial (NHBE) cells. TPA (0.1 to 100 nM) did not enhance the clonal growth rate for any of the cell lines. As little as 3 nM TPA induced the NHBE cells to undergo terminal squamous differentiation and thus completely inhibited their proliferation; in contrast, none of the carcinoma cell lines was significantly inhibited at this concentration, and they all continued to proliferate in as much as 100 nM TPA. To determine if this lack of TPA inhibition of clonal growth reflected resistance to TPA induction of terminal squamous differentiation, we measured the ability of TPA to induce cross-linked envelope formation and to increase plasminogen activator activity in four carcinoma cell lines. Cross-linked envelopes were not induced in two lines, and only a small number were induced in the other two lines relative to NHBE cells; plasminogen activator activity was induced in NHBE cells but not in any of the cell lines.

Cell Division↗
PubMed1984

Effects of characteristic x-rays on assay of I-123 by dose calibrator.

Large differences in dose-calibrator readings are obtained if "high-purity" I-123 is assayed in different containers. Large correction factors are necessary for assaying another isotope of iodine, I-125, in a dose calibrator, because of absorption of the low-energy (28.4-keV, weighted mean) emissions. We found that up to 70% of the dose-calibrator response to I-123 can be due to characteristic x-rays with energies exactly the same as those emitted by I-125, and that dose-calibrator response to I-123 is also strongly affected by the absorption properties of the vial. An appropriate method to define I-123 activity uses a gamma camera with a medium-energy collimator to establish correction factors for dose-calibrator assay of I-123 in different containers. Correction factors for a plastic syringe and a thick-wall glass vial, were determined using this method. Measurement of I-123 activity in a copper absorber will eliminate the response to x-rays, and the gamma camera is useful in establishing the necessary correction factors.

Calibration↗