PubMed Health⌕ Search

Biomedical subjects

A L Brooks

Publications and source records attributed to A L Brooks.

At least 19 recordsLinked to original sources
PubMed1996

Clastogenic effects of defined numbers of 3.2 MeV alpha particles on individual CHO-K1 cells.

Research to determine the effects of defined numbers of alpha particles on individual mammalian cells is helpful in understanding risks associated with exposure to radon. This paper reports the first biological data generated using the single-particle/single-cell irradiation system developed at Pacific Northwest Laboratory. Using this apparatus, CHO-K1 cells were exposed to controlled numbers of 3.2 MeV alpha particles, and biological responses of individual cells to these irradiations were quantified. Chromosomal damage, measured by the induction of micronuclei, was evaluated after no, one, two, three or five particle traversals. Exposures of up to five alpha particles had no influence on the total numbers of cells recovered for scoring. With increased numbers of alpha particles there was a decrease in the ratio of binucleated to mononucleated cells of 3.5%/hit, suggesting that alpha particles induced dose-dependent mitotic delay. A linear hit-response relationship was observed for micronucleus induction: Micronuclei/binucleated cell = 0.013 +/- 0.036 + (0.08 +/- 0.013) x D, where D is the number of particles. When the estimated dose per alpha-particle traversal was related to the frequency of induced micronuclei, the amount of chromosomal damage per unit dose was found to be similar to that resulting from exposures to alpha particles from other types of sources. Approximately 72% of the cells exposed to five alpha particles yield no micronuclei, suggesting the potential for differential sensitivity in the cell population. Additional studies are needed to control biological variables such as stage of the cell cycle and physical parameters to ensure that each cell scored received the same number of nuclear traversals.

Alpha Particles↗
PubMed1995

Inhaled radon-induced genotoxicity in Wistar rat, Syrian hamster, and Chinese hamster deep-lung fibroblasts in vivo.

This study was performed (1) to provide a comparison of the genotoxic effects of inhaled radon and radon progeny, referred to as radon in this paper, among three species of rodents: Wistar rats, Syrian hamsters, and Chinese hamsters; (2) to determine if initial chromosome damage was related to the risk of induction of lung cancer; and (3) to evaluate the tissue repair and long-term presence of cytogenetic damage in respiratory tract cells. These species were selected because Syrian hamsters are very resistant to radon induction of lung cancer and Wistar rats are sensitive; no literature is available on the in vivo effects of radon in the Chinese hamster. Exposure-response relationships were established for the rats and Syrian hamsters while the Chinese hamsters received a single exposure of radon. At 4 h (0.2 days), 15 days, and 30 days after the highest WLM exposure to radon, Wistar rats, Chinese hamsters, and Syrian hamsters were killed, and lung fibroblasts were isolated and grown in culture to determine the frequency of induced micronuclei. Animals at each level of exposure showed an increase in the frequency of micronuclei relative to that in controls (P < 0.05). The exposure-response relationship data for rats and Syrian hamsters killed 0.2 days after the end of exposure were fit to linear equations (micronuclei/1000 binucleated cells = 15.5 +/- 14.4 + 0.53 +/- 0.06 WLM and 38.3 +/- 15.1 + 0.80 +/- 0.08 WLM, respectively). For the single exposure level used (496 WLM) in Chinese hamsters killed at 0.2 days after exposure, the frequency of micronuclei/1000 binucleated cells/WLM was 1.83 +/- 0.02. A comparison of the sensitivity for induction of micronuclei/WLM illustrated that Chinese hamsters were three times more sensitive than rats. The Syrian hamsters also showed a significantly elevated response (P < 0.05) relative to rats. These data suggest that initial chromosome damage is not the major factor responsible for the high rate of radon-induced cancer in rats relative to Syrian hamsters. The frequency of micronuclei in radon-exposed rats, Syrian hamsters, and Chinese hamsters significantly decreased (P < 0.05) as a function of time after the exposure. The rate of loss of damaged cells from the lung was greatest in the Chinese hamsters, followed by Wistar rats and Syrian hamsters, respectively.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants, Radioactive↗
PubMed1995

The role of dose rate in the induction of micronuclei in deep-lung fibroblasts in vivo after exposure to cobalt-60 gamma rays.

To evaluate the influence of low-dose-rate exposures on biological damage, it is necessary to have cells that can be maintained in the same stage of the cell cycle for long periods. Normal rat lung fibroblasts represent a stable cell type with a slow turnover rate in vivo. These cells can be stimulated to divide by placing them in tissue culture. Therefore, a constant cell population can be exposed over a protracted time and stimulated to divide, and the cytogenetic damage can be evaluated at the first cell division after exposure. By placing rats at different distances from a 60Co source, they were exposed to graded doses of gamma rays--0.0, 3.9, 7.4 and 11.3 Gy--protracted over either 4 or 67 h. Fibroblasts were isolated from the lung and cultured for 24 h; after cytochalasin B was added, the cells were cultured for an additional 69 to 72 h. The percentage binucleated cells in fibroblasts of animals exposed for 4 or 67 h was 47.1 +/- 4.3 and 62.1 +/- 3.9. There was no influence of dose on the percentage binucleated cells, but the fraction of cells that divided at 67 h was significantly higher (P < 0.05) than observed at 4 h. Cells were scored for micronuclei on coded slides. The dose-response data from animals exposed for 4 and 67 h were fitted to the following linear dose-response relationships, where D = dose; micronuclei/binucleated cell = 0.02 +/- 0.03 + 2.38 +/- 0.44 x 10(-2) D, and micronuclei/binucleated cell = 0.01 +/- 0.06 + 1.01 +/- 0.10 x 10(-2) D, respectively. The r2 values for the two curves were 0.67 and 0.91, indicating the goodness of fit for the data for the 4- and 67-h treatments. The slopes were different from zero and each other at the P < 0.05 level of significance. The effectiveness of the 60Co exposure decreased as the dose rate decreased. At dose rates below 0.17 Gy/h, the effectiveness remained constant over the range of doses and dose rates used. Comparing the slope of the dose response for the lowest exposure rate to that from information published previously, the dose-rate effectiveness factor was 6.14 +/- 0.65 for the induction of micronuclei in deep-lung fibroblasts.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1994

Pulmonary toxicity of inhaled diesel exhaust and carbon black in chronically exposed rats. Part I: Neoplastic and nonneoplastic lung lesions.

This study compared the pulmonary carcinogenicities and selected noncancer effects produced by chronic exposure of rats at high rates to diesel exhaust and carbon black. The comparison was intended to provide insight into the likely importance of the mutagenic organic compounds associated with the soot portion of diesel exhaust in inducing pulmonary carcinogenicity in diesel exhaust-exposed rats. The role of the organic fraction has become important in judging the usefulness of the substantial data base on carcinogenicity in rats for predicting lung cancer risk for humans, and for determining the most appropriate method of extrapolating results across species and exposure concentrations. Rats were exposed chronically to either diesel exhaust or carbon black, which served as a surrogate for diesel exhaust soot with much reduced mutagenic activity associated with its organic fraction. The sequestration of particles in the lung and the induction of pulmonary neoplasia and non-neoplastic changes in the lung were compared in detail. Samples also were provided to collaborators to examine adduct formation in lung DNA and hemoglobin. Approximately 140 female and 140 male F344/N rats were exposed for 16 hours per day, 5 days per week for up to 24 months, beginning at eight weeks of age, to diesel exhaust or carbon black at 2.5 mg or at 6.5 mg particles/m3 of air, or to clean air as controls. The diesel exhaust was generated by light-duty engines burning certification fuel and operating on an urban-duty cycle. The carbon black was selected because it had particle size and surface area characteristics similar to those of diesel exhaust soot, but markedly less mutagenic activity associated with its organic fraction when analyzed using procedures typically used in studies of diesel soot. Rats were killed after 3, 6, 12, 18, or 23 months of exposure to measure lung and lung-associated lymph node burdens of particles, lung weight, bronchoalveolar lavage indicators of inflammation, DNA adducts in whole lung and alveolar type II cells, and chromosome injury in circulating lymphocytes, and to perform histopathologic assessment. In addition, after 3 and 18 months of chronic exposure, one group of rats was acutely exposed to radiolabeled carbon black particles or to fluorescent microspheres. These exposures were conducted to examine the clearance of radiolabeled particles and the sequestration of the fluorescent microspheres in the lungs. These experiments provided information on clearance overload and particle dosimetry. The growth characteristics of lung neoplasms also were examined by transplanting neoplastic cells into athymic mice.(ABSTRACT TRUNCATED AT 400 WORDS)

Air Pollutants, Occupational↗
PubMed1994

Effectiveness of radon relative to acute 60Co gamma-rays for induction of micronuclei in vitro and in vivo.

Because radon and its progeny (referred to collectively here as radon) emit alpha particles with a wide range of energies, as well as beta particles and gamma-rays, it is important to quantitate the relationship between initial damage induced by radon and that by acute low-LET radiation. We have evaluated dose-response relationships for induction of micronuclei both in vivo and in vitro following exposure to radon or 60Co. To determine if isolation procedures altered the cells' responsiveness to 60Co gamma-ray exposures, animals were exposed before cell isolation, or cells were isolated and then exposed. The data were described by linear dose-response functions and were not significantly different when the radiation exposure was in vivo or in vitro (respectively micronuclei/1000 binucleated cells = 1.6 +/- 6.5 + 62 +/- 2.7 D; micronuclei/1000 binucleated cells = 15.4 +/- 26.0 + 54.6 +/- 11.4 D, where D is in Gy). Primary rat lung fibroblasts (RLF) or Chinese hamster ovary (CHO-K1) cells were exposed in vitro to either radon or 60Co gamma-rays. Radon was 10.9 +/- 2.6 and 12.5 +/- 2.4 times as effective per Gy of radiation dose in producing micronuclei as was 60Co in RLF and CHO-K1 cells respectively. To determine the relative biological effectiveness of in vivo radon exposure, animals were exposed to either radon or 60Co, and lung fibroblasts were isolated and evaluated for radiation-induced micronuclei. In vivo radon exposure was 10.6 +/- 1.0 times as effective as acute whole-body 60Co exposure in producing micronuclei in lung fibroblasts. Different cell lines and exposure conditions resulted in similar effectiveness factors. Such ratios help evaluate the biological damage, hazard and risk associated with radon inhalation.

Animals↗
PubMed1994

Micronuclei induced by radon and its progeny in deep-lung fibroblasts of rats in vivo and in vitro.

Genotoxic damage induced by radon and its progeny was investigated using the micronucleus assay in deep-lung fibroblasts to compare the response induced in vitro with that induced from inhalation of radon and its progeny in vivo. Male Wistar rats were exposed to 0, 115, 213 and 323 working-level months (WLM) of radon and its progeny by inhalation. After sacrifice, the cells were isolated and grown in culture, and the frequency of micronuclei was determined. A linear increase in the frequency of micronuclei was measured as a function of exposure [micronuclei/1000 binucleated cells = (29 +/- 9) + (0.47 +/- 0.04) WLM]. To compare exposure in WLM to dose in mGy, and to study how cell proliferation influences the way inhalation of radon and its progeny induces micronuclei, lung fibroblasts were isolated and exposed in vitro to graded doses from radon and its progeny after either 16 or 96 h in tissue culture. Cell cycle stage at the time of exposure was determined using flow cytometry. Primary lung fibroblasts exposed as either nondividing or dividing cells showed dose-dependent increases in micronuclei [micronuclei/1000 binucleated cells = (33 +/- 40) + (593 +/- 68)D and micronuclei/1000 binucleated cells = (27 +/- 69) + (757 +/- 88)D, respectively, where D is dose in Gy]. Results showed no significant influence (P = 0.20) of cell proliferation at the time of exposure on the frequency of micronuclei induced by radon and its progeny. Comparing dose-response relationships for nondividing cells to the exposure response for cells exposed by inhalation of radon and its progeny, it was estimated that a 1-WLM exposure in vivo caused the same amount of cytogenetic damage as produced by 0.79 mGy in vitro. In vivo/in vitro research using the micronucleus assay in lung fibroblasts serves as a powerful tool to estimate effective dose to cells in the respiratory tract after inhalation of radon and its progeny. Such studies form the basis for understanding the relationship between exposure, dose and biological damage.

Administration, Inhalation↗
PubMed1992

In vitro activity of silicon carbide whiskers in comparison to other industrial fibers using four cell culture systems.

Silicon carbide whiskers (SiCW) and continuous glass filaments are important components of composite materials having potentially widespread use in the automotive, aerospace, and power generation industries. We determined the in vitro activity of three well-characterized samples of silicon carbide whiskers and a continuous glass filament sample in four different cellular assays and compared this to the activities of UICC crocidolite, JM Code 100 glass microfiber, and erionite in the same assay systems. The SiCW had a diameter range of 0.32-0.75 microns and a length range of 4.5-20.1 microns. The SiCW was significantly toxic; on a mass basis, one SiCW sample was more toxic than crocidolite; however, JM Code 100 glass microfiber, which is not toxic in vivo (i.e., it does not cause fibrogenesis or carcinogenesis when inhaled), was also more toxic than crocidolite. The glass filament sample was the least cytotoxic of all the samples tested. On a fiber number basis, all three SiCW samples were more toxic than crocidolite. The results of our study showed that SiCW exhibits significant in vitro biological reactivity. Thus, despite the caution that must be exercised in extrpolating the results of in vitro studies to conclusions about in vivo health effects, SiCW should be considered toxic until further toxicological data are available.

Aluminum Silicates↗
PubMed1992

Distribution and biological effects of inhaled 239Pu(NO3)4 in cynomolgus monkeys.

Twenty male cynomolgus monkeys were exposed by inhalation either to an aerosol of 239Pu(NO3)4 to produce projected initial lung burdens of either 40, 10, or 4 kBq or to a carrier aerosol as a control. Animals died or were sacrificed at 0.01, 1, 3, 6, 12, 24, 40, and 99 months after inhalation, and the distribution and biological effects of the 239Pu were determined. The 239Pu cleared efficiently from the lungs so that less than 0.05 kBq remained at 99 months after exposure to 40 kBq. Total skeletal 239Pu activity was nearly constant after the first year, but the fraction of the body burden in skeleton at sacrifice increased with time up to 99 months because of clearance from other organs. Plutonium in the liver increased to a peak at 1 year and then decreased to about 10% of the peak value at 99 months. Plutonium in the testes was localized in the interstitial tissue with only 0.01 to 0.002% of the projected lung burden remaining in testes at 99 months after inhalation. Three animals exposed to 40 kBq of 239Pu died of radiation-related pulmonary pneumonitis and fibrosis. A primary papillary adenocarcinoma of the lung was identified in one animal exposed to 40 kBq initial lung burden and sacrificed 99 months after inhalation. The frequency of chromosome aberrations in blood lymphocytes was significantly elevated only in monkeys with projected deposits of 40 kBq of 239Pu. There was no change in aberration frequency in other exposure groups as a function of inhaled activity, time after exposure, or calculated total dose to the lungs. Only in monkeys that had marked radiation-induced pathological changes in the lung did the frequency of chromosome-type aberrations increase significantly, to a value about twice the control level. In cynomolgus monkeys, chromosome aberration frequency in blood lymphocytes is not a good indicator of radiation dose or damage from inhaled soluble plutonium.

Administration, Inhalation↗
PubMed1991

Effects of beryllium metal particles on the viability and function of cultured rat alveolar macrophages.

The physicochemical properties of particles influence their in vivo toxicity following deposition in the respiratory tract. To evaluate the relative contributions of mass and surface area to particle-induced toxicity, rat pulmonary alveolar macrophages (PAM) were exposed to four types of particles in vitro. We used three beryllium metal samples: relatively large (Be-II) and relatively small (Be-V) sized fractions of beryllium metal obtained from an aerosol cyclone, and a beryllium metal aerosol generated by laser vaporization of bulk beryllium metal in an argon atmosphere (Be-L). We also used glass beads (GB) as a negative control particle. End points examined included cell viability, determined by trypan blue dye exclusion, and changes in phagocytic ability, measured by counting the number of sheep red blood cells internalized by the PAM. Phagocytic ability was inhibited by exposure to beryllium particles at concentrations that did not cause appreciable cell death. Results describing effects based on the mass concentration of particles in culture medium were transformed by the amount of specific surface area of the particles to permit the expression of toxicity relative to the amount of particle surface per unit volume of culture medium. On a mass basis, the order of particle-related cytotoxicity was Be-L greater than Be-V greater than Be-II greater than GB, and for inhibition of phagocytosis, the order was Be-L approximately Be-V greater than Be-II greater than GB. When analyzed on a specific surface area basis, the cytotoxicity of the different materials became more similar in a fashion that was largely predicted by the amount of surface of the particles administered. However, because differences in specific surface area among the beryllium particle samples did not entirely predict cytotoxicity, we concluded that factors in addition to specific surface area influenced the expression of toxic effects in cultures of PAM exposed to beryllium metal.

Animals↗
PubMed1990

Chromosome damage in rat pulmonary alveolar macrophages following ozone inhalation.

To determine whether ozone is clastogenic at environmentally relevant exposure levels, rats were exposed for 6 h to 0.0, 0.12, 0.27, or 0.80 ppm ozone. The alveolar macrophages were isolated from animals sacrificed 28 h after the end of the exposure. The mitotic index and frequency of chromosome aberrations were determined. No change in the mitotic index was detected following 0.12 ppm ozone exposure. A significant decrease in mitotic index was observed after exposure to 0.27 ppm ozone; a significant (4-fold) increase in the frequency of dividing macrophages was detected following exposure to 0.8 ppm ozone. Only chromatid-type aberrations were observed. There was a significant increase in the frequency of cells with chromatid gaps and in the frequency of cells with chromatid deletions. Animals exposed to 0.27 ppm ozone had the highest proportion of cells with chromatid deletions (0.172) relative to background level (0.028). No exchanges or chromosome-type aberrations were detected in any of the animals. These data suggest that ozone, at relatively low levels, is clastogenic in macrophages from exposed rats.

Administration, Inhalation↗
PubMed1990

The combined effects of alpha-particles and X-rays on cell killing and micronuclei induction in lung epithelial cells.

Understanding how cellular damage produced by high-linear energy transfer (LET) radiation interacts with that produced by low-LET is important both in radiation therapy and in evaluating risk. To study such interactions, rat lung epithelial cells (LEC) were grown on Mylar films and exposed to both X-rays and alpha-particles, separately or simultaneously. Cell killing, and the numbers of binucleated cells and micronuclei, were measured as indicators of damage. X-rays and alpha-particles given separately caused dose-related increases in cell cycle time, with alpha-particles producing greater mitotic delay than X-rays. Damage from alpha-particles and X-rays given simultaneously did not interact to alter further the cell cycle. Cell survival data following exposure to X-rays and alpha-particles, combined or individually, were fitted by linear-quadratic models. Survival curves following exposure to alpha-particles only, or to 1.0 Gy alpha-particles plus graded X-ray doses, were adequately described using only the linear (alpha) term of a linear-quadratic model with alpha coefficients of 0.9 +/- 0.04 and 1.03 +/- 0.18 Gy-1, respectively. Survival following exposure to X-rays only or to 0.06 Gy alpha-particles combined with X-rays was best fitted using both alpha and beta terms of the linear-quadratic model (0.12 +/- 0.03)D + (0.007 +/- 0.002)D2 and (0.57 +/- 0.08)D + (0.3 +/- 0.02)D2, respectively. The numbers of micronuclei produced by exposure to alpha-particles or X-rays alone increased linearly with dose, with slopes of 0.48 +/- 0.07 and 0.19 +/- 0.05 micronuclei/binucleated cell per Gy for alpha and X-rays, respectively. Simultaneous exposure to graded levels of X-rays and a constant alpha dose of either 1.0 or 0.06 Gy increased micronuclei frequency, with a slope of 0.74 +/- 0.05 or 0.58 +/- 0.04 micronuclei/binucleated cell per Gy, respectively. These slopes are similar to that produced by alpha-particles alone. These studies demonstrated that both cell killing and the induction of micronuclei were increased by combined exposures compared with that predicted for separate exposures.

Alpha Particles↗
PubMed1989

In vitro genotoxicity of dyes present in colored smoke munitions.

Genetic toxicology studies were conducted on organic dyes and mixtures used in colored smoke munitions. The dyes studied included Solvent Red 1; two different batches (Lot 1 and Lot 2) of Disperse Red 11; terephthalic acid; and a mixture of 25 parts Solvent Red 1, 5 parts Disperse Red 11, and 16 parts terephthalic acid. The dyes were evaluated for their ability to produce mutations in Salmonella bacterial strains and in Chinese hamster ovary (CHO) cells. The dyes were also tested in CHO cells to determine cytotoxicity and the induction of sister chromatid exchanges and chromosome aberration. None of the dyes were genotoxic in the standard Ames assay using bacterial strain TA1535 or TA100 with or without the addition of S-9 or in TA98 and TA1538 without S-9. With S-9, Disperse Red 11 (Lot 2) showed significant mutagenic activity in TA98 and TA1538 which increased as a function of S-9 concentration. However, the maximum level of mutagenic activity detected was low (3.8 revertants/micrograms). The azo dye Solvent Red 1 was also negative in a pre-incubation assay designed to reduce azo compounds to free amines. Solvent Red 1 was cytotoxic to mammalian cells, caused a significant increase in SCE, but was not mutagenic or clastogenic. Disperse Red 11 (Lot 1 and Lot 2) were not cytotoxic or clastogenic but produced an increase in cell cycle time and SCE frequency. Only Disperse Red 11 (Lot 2) increased mutations in the CHO/hypoxanthine-guanine phosphoribosyltransferase (HGPRT) assay. The mutagenic activity of the dye mixture was not significant, suggesting no synergistic interaction between the dyes. These studies demonstrated that none of the dyes was clastogenic and that a contaminant in Disperse Red 11 (Lot 2) may be responsible for the weak mutagenic activity in both mammalian and bacterial cell systems.

Animals↗
PubMed1989

Cytogenetic effects of cigarette smoke on pulmonary alveolar macrophages of the rat.

To determine accurately the potential genetic damage induced by toxic inhaled agents, the cells that receive a high concentration of such agents should be analyzed. Pulmonary alveolar macrophages (PAMs) represent such cells. We compared the cytogenetic effects of cigarette smoke on PAMs of rats exposed repeatedly by different methods. This study was part of a larger investigation of the health effects resulting from different methods of exposing rats to cigarette smoke. Fischer 344/N male rats (4/group) were randomly selected from five different exposure groups: 1) nose-only sham-exposed (air) control, 2) whole-body sham-exposed control, 3) nose-only intermittent, 4) nose-only continuous, and 5) whole-body continuous. The rats were exposed 6 hr/day, 5 days/week for 22-24 days. All smoke-exposed rats received the same daily concentration x time product (600 mg.hr.m-3 for the first week, 1200 mg.hr.m-3 thereafter) of cigarette smoke. Rats were injected intraperitoneally with colchicine at the end of exposure. PAMs were obtained by lung lavage and chromosomal damage was measured. Highly significant smoke-induced differences in both structural and numerical aberrations were observed in continuously exposed rats vs. sham controls, regardless route of exposure. The structural aberrations observed were chromatid-type deletions. Both hypoploid and hyperploid cells were detected. Our data suggest that cigarette smoke is clastogenic and may disrupt spindle-fiber formation. These activities may play a role in the induction of human carcinogenesis caused by cigarette smoke exposure.

Animals↗
PubMed1989

The induction of chromosome damage in CHO cells by beryllium and radiation given alone and in combination.

Studies were conducted to determine the effects of BeSO4 or X rays, alone and in combination, on cell cycle kinetics, cell killing, and the production of chromosome aberrations in Chinese hamster ovary (CHO) cells. The concentration of BeSO4 required to kill 50% of CHO cells exposed to BeSO4 for 20 h was determined to be 1.1 mM with 95% confidence intervals of 0.72 to 1.8 mM. During the last 2 h of the 20-h beryllium treatment (0.2 and 1.0 mM), cells were exposed to 0.0, 1.0, or 2.0 Gy of X rays. Exposure to either BeSO4 or X rays produced a change in cell cycle kinetics which resulted in an accumulation of cells in the G2/M stage of the cell cycle. However, combined exposure to both agents resulted in a block similar to that observed following exposure to X rays only. The background level of chromosome damage was 0.05 +/- 0.015 aberrations/cell in the CHO cells. Seven hours after the end of exposure to 0.2 and 1.0 mM beryllium, 0.03 +/- 0.003 and 0.09 +/- 0.02 aberrations/cell, respectively, were observed. The data for chromosome aberrations following X-ray exposure were fitted to a linear model with a coefficient of 0.14 +/- 0.01 aberrations/cell/Gy. When beryllium was combined with the X-ray exposure the interactive response was predicted by a multiplicative model and was significantly higher (P less than 0.05) than predicted by an additive model. The influence of time after radiation exposure on the interaction between beryllium and X rays was also determined. No interaction between beryllium and X-ray exposure in the induction of chromosome-type aberrations (P greater than 0.05) was detected. The frequency of chromatid-type exchanges and total aberrations was significantly higher (P less than 0.05) in the radiation plus beryllium-exposed cells when compared to cells exposed to X rays only, at both 9 and 12 h after X-ray exposure. These data suggest that the multiplicative interaction may be limited to cells in the S and G2 stages of the cell cycle.

Animals↗
PubMed1988

The cytogenetic and hepatotoxic effects of dioxin on mouse liver cells.

The cytogenetic and hepatotoxic effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on mouse liver cells were investigated. Male C57BL/6J strain mice, which have TCDD receptors, were given single intraperitoneal injections of 25, 37.5, 75 and 150 micrograms of TCDD/kg body weight or corn oil carrier alone. Two-thirds hepatectomies were carried out at 1 or 7 days after injection and chromosomal aberrations and mitotic indexes of the regenerating hepatocytes were scored 54 hr after hepatectomy. Liver sections from additional intact mice were studied for TCDD-hepatotoxicity at 1, 7 and 30 days after injection. The three high doses of TCDD caused hepatotoxicity with necrosis of liver cells and focal architectural collapse by 30 days after injection. No evidence was obtained of an increase in the frequency of chromosomal structural aberrations at doses that allowed sufficient mitotic activity for cytogenetic evaluation. We conclude that TCDD is not a clastogen for mouse hepatocytes, although high doses cause marked hepatocellular necrosis.

Animals↗
PubMed1988

Current status of cytogenetic procedures to detect and quantify previous exposures to radiation.

The estimation of the magnitude of a dose of ionizing radiation to which an individual has been exposed (or of the plausibility of an alleged exposure) from chromosomal aberration frequencies determined in peripheral blood lymphocyte cultures is a well-established methodology, having first been employed over 25 years ago. The cytogenetics working group has reviewed the accumulated data and the possible applicability of the technique to the determination of radiation doses to which American veterans might have been exposed as participants in nuclear weapons tests in the continental U.S.A. or the Pacific Atolls during the late 1940s and 1950s or as members of the Occupation Forces entering Hiroshima or Nagasaki shortly after the nuclear detonations there. The working group believes that with prompt peripheral blood sampling, external doses to individuals of the order of about 10 rad (or less if the exposure was to high-LET radiation) can accurately be detected and measured. It also believes that exposures of populations to doses of the order of maximum permissible occupational exposures can also be detected (but only in populations; not in an individual). Large exposures of populations can also be detected even several decades after their exposure, but only in the case of populations, and of large doses (of the order of 100 to several hundred rad). The working group does not believe that cytogenetic measurements can detect internal doses from fallout radionuclides in individuals unless these are very large. The working group has approached the problem of detection of small doses (less than or equal to 10 or so rad) sampled decades after the exposure of individuals by using a Bayesian statistical approach. Only a preliminary evaluation of this approach was possible, but it is clear that it could provide a formal statement of the likelihood that any given observation of a particular number of chromosomal aberrations in a sample of any particular number of lymphocytes actually indicates an exposure to any given dose of radiation. It is also clear that aberration frequencies (and consequently doses) would have to be quite high before much confidence could be given to either exposure or dose estimation by this method, given the approximately 3 decades of elapsed time between the exposures and any future blood sampling.(ABSTRACT TRUNCATED AT 400 WORDS)

Abnormalities, Radiation-Induced↗
PubMed1988

The structure-function relationships of nitrofluorenes and nitrofluorenones in the Salmonella mutagenicity and CHO sister-chromatid exchange assays.

Nitrofluorenes and nitrofluorenones are bacterial mutagens and are detected in a variety of environmental pollution sources. We tested a series of nitrosubstituted fluorenes and fluorenones for their genotoxicity using both Salmonella bacteria and Chinese hamster ovary (CHO) cells to determine if structure-function relationships observed in bacteria for mutation induction are similar to those for mutations and SCE induction in mammalian (CHO) cells. The compounds studied were 2-nitrofluorene (2-NF), 2,7-dinitrofluorene (2,7-DNF), 3-nitrofluorenone (3-NFone), 2-nitrofluorenone (2-NFone), 2,7-dinitrofluorenone (2,7-DNFone), 2,4,7-trinitrofluorenone (2,4,7-TNFone), and 2,4,5,7-tetranitrofluorenone (2,4,5,7-TNFone). In bacteria, the presence of carbonyl group to convert mono-nitrofluorenes to nitrofluorenones and the addition of a second nitro group to either mono-nitrofluorene or fluorenone to form the dinitro compounds increased mutagenic activity in the Ames test. Location of the nitro group relative to the carbonyl group was important in enhancing mutagenic activity as 2-nitrofluorenone was more mutagenic than 3-nitrofluorenone. In CHO cells, the di-, tri- and tetra-nitrofluorenones were cytotoxic and delayed the progression of CHO cells through the cell cycle. The degree of the cytotoxicity could be decreased by the addition of S9. None of the compounds produced mutations when tested in the CHO/HGPRT mutation assay with the addition of S9. Nonetheless, the current study did show that these compounds, both with and without the activation by S9, can interact with the DNA and produce SCE in CHO cells. The addition of a carbonyl group had no influence on SCE frequency since both 2-nitrofluorene and 2-nitrofluorenone induced a similar frequency of SCE either with or without S9. Additional nitro groups, forming di-, tri- or tetra-nitrofluorenones, increased the frequency of SCE induced, especially when tested with S9 which limits cytotoxicity. The addition of a single nitro group to 2-nitrofluorenone did not change the SCE frequency but did cause a large increase in the frequency of mutations in bacteria. In contrast, 2,4,7-TNFone and 2,4,5,7-TNFone were less mutagenic than the 2,7-DNFone in bacteria but were more effective in production of SCE in CHO cells. This study illustrates that structure-function relationships are dependent on both the compounds tested and the type of genetic change induced.

Animals↗