Doses from beta radiation in sensitive layers of human lung and dose conversion factors due to <Superscript>222</Superscript>Rn/<Superscript>220</Superscript>Rn progeny

Great deal of work has been devoted to determine doses from alpha particles emitted by ²²²Rn and ²²⁰Rn progeny. In contrast, contribution of beta particles to total dose has been neglected by most of the authors. The present work describes a study of the detriment of ²²²Rn and ²²⁰Rn progeny to the human lung due to beta particles. The dose conversion factor (DCF) was introduced to relate effective dose and exposure to radon progeny; it is defined as effective dose per unit exposure to inhaled radon or thoron progeny. Doses and DCFs were determined for beta radiation in sensitive layers of bronchi (BB) and bronchioles (bb), taking into account inhaled ²²²Rn and ²²⁰Rn progeny deposited in mucus and cilia layer. The nuclei columnar secretory and short basal cells were considered to be sensitive target layers. For dose calculation, electron-absorbed fractions (AFs) in the sensitive layers of the BB and bb regions were used. Activities in the fast and slow mucus of the BB and bb regions were obtained using the LUNGDOSE software developed earlier. Calculated DCFs due to beta radiation were 0.21 mSv/WLM for ²²²Rn and 0.06 mSv/WLM for ²²⁰Rn progeny. In addition, the influence of Jacobi room parameters on DCFs was investigated, and it was shown that DCFs vary with these parameters by up to 50%.     

Lung dosimetry of inhaled radon progeny in mice

Biological response of exposure to radon progeny has long been investigated, but there are only few studies in which absorbed doses in lungs of laboratory animals were estimated. The present study is the first attempt to calculate the doses of inhaled radon progeny for mice. For reference, the doses for rats and humans were also computed with the corresponding models. Lung deposition of particles, their clearance, and energy deposition of alpha particles to sensitive tissues were systematically simulated. Absorbed doses to trachea and bronchi, bronchioles and terminal bronchioles, alveolar-interstitial regions, and whole lung were first provided as a function of monodisperse radon progeny particles with an equilibrium equivalent radon concentration of 1?Bq?m^?3 (equilibrium factor, 0.4 and unattached fraction, 0.01). Based on the results, absorbed doses were then calculated for (1) a reference mine condition and (2) a condition previously used for animal experiments. It was found that the whole lung doses for mice, rats, and humans were 34.8, 20.7, and 10.7?nGy (Bq?m^?3)^?1?h^?1 for the mine condition, respectively, while they were 16.9, 9.9, and 6.5?nGy (Bq?m^?3)^?1?h^?1 for the animal experimental condition. In both cases, the values for mice are about 2 times higher than those for rats, and about 3 times higher than those for humans. Comparison of our data on rats and humans with those published in the literature shows an acceptable agreement, suggesting the validity of the present modeling for mice. In the future, a more sophisticated dosimetric study of inhaled radon progeny in mice would be desirable to demonstrate how anatomical, physiological, and environmental parameters can influence absorbed doses.     

Deposition of radon progeny on skin surfaces and resulting radiation doses in radon therapy

In the Gastein valley, Austria, radon-rich thermal water and air have been used for decades for the treatment of various diseases. To explore the exposure pathway of radon progeny adsorbed to the skin, progeny activities on the skin of patients exposed to thermal water (in a bathtub) and hot vapour (in a vapour chamber) were measured by alpha spectrometry. Average total alpha activities on the patients’ skin varied from 1.2 to 4.1 Bq/cm² in the bathtub, and from 1.1 to 2.6 Bq/cm² in the vapour bath. Water pH-value and ion concentration did affect radon progeny adsorption on the skin, whereas skin greasiness and blood circulation did not. Measurements of the penetration of deposited radon progeny into the skin revealed a roughly exponential activity distribution in the upper layers of the skin. Based on the radon progeny surface activity concentrations and their depth distributions, equivalent doses to different layers of the skin, in particular to the Langerhans cells located in the epidermis, ranged from 0.12 mSv in the thermal bath to 0.33 mSv in the vapour bath, exceeding equivalent doses to the inner organs (kidneys) by inhaled radon and progeny by about a factor 3, except for the lung, which receives the highest doses via inhalation. These results suggest that radon progeny attachment on skin surfaces may play a major role in the dosimetry for both thermal water and hot vapour treatment schemes.     

In vitro exposure of mammalian cells to radon: dosimetric considerations

We have developed a model to calculate the dose to the cell nucleus in cells exposed in suspension to radon and/or radon progeny. The model addresses the influence of (1) different radiation qualities and energies in the irradiation milieu; (2) the contribution to dose from radioactivity in the medium surrounding the cell after exposure to the radon gas as well as that from excess radon progeny associated with the cell; (3) the geometry of the cell and of the radiosensitive target, the cell nucleus; (4) the intracellular localization of the radionuclides; (5) attenuation of the alpha particles by the cytoplasm; (6) the radionuclide concentrations in the medium; and (7) the length of exposure. Investigation of the influence of these various parameters was made using an irradiation system in which cells were exposed to 212Bi, which decays to stability with the emission of an alpha particle (either 6.05 or 8.78 MeV). The information from these studies was then used to develop the system further for more complex systems in which 222Rn and its progeny are present. The model takes into account the contribution of dose from different radiation sources using scintillation counts of the medium and the cells, and it is useful for calculations of dose in situations where cells are exposed in suspension culture.     

Age-dependent inhalation doses to members of the public from indoor short-lived radon progeny

The main contribution of radiation dose to the human lungs from natural exposure originates from short-lived radon progeny. In the present work, the inhalation doses from indoor short-lived radon progeny, i.e., ²¹⁸Po, ²¹⁴Pb, ²¹⁴Bi, and ²¹⁴Po, to different age groups of members of the public were calculated. In the calculations, the age-dependent systemic biokinetic models of polonium, bismuth, and lead published by the International Commission on Radiological Protection (ICRP) were adopted. In addition, the ICRP human respiratory tract and gastrointestinal tract models were applied to determine the deposition fractions in different regions of the lungs during inhalation and exhalation, and the absorption fractions of radon progeny in the alimentary tract. Based on the calculated contribution of each progeny to equivalent dose and effective dose, the dose conversion factor was estimated, taking into account the unattached fraction of aerosols, attached aerosols in the nucleation, accumulation and coarse modes, and the potential alpha energy concentration fraction in indoor air. It turned out that for each progeny, the equivalent doses to extrathoracic airways and the lungs are greater than those to other organs. The contribution of ²¹⁴Po to effective dose is much smaller compared to that of the other short-lived radon progeny and can thus be neglected in the dose assessment. In fact, 90 % of the effective dose from short-lived radon progeny arises from ²¹⁴Pb and ²¹⁴Bi, while the rest is from ²¹⁸Po. The dose conversion factors obtained in the present study are 17 and 18 mSv per working level month (WLM) for adult female and male, respectively. This compares to values ranging from 6 to 20 mSv WLM^?1 calculated by other investigators. The dose coefficients of each radon progeny calculated in the present study can be used to estimate the radiation doses for the population, especially for small children and women, in specific regions of the world exposed to radon progeny by measuring their concentrations, aerosol sizes, and unattached fractions.     

Microdosimetric calculation of absorption fraction and the resulting dose conversion factor for radon progeny

It is an established fact that radon progeny can induce lung cancers. However, there is a well-known discrepancy between the epidemiologically derived dose conversion factor for radon progeny (4 mSv/WLM) and the dosimetrically derived value (15 mSv/WLM) (mSv is a unit of the dose while WLM is a unit of exposure to radon progeny). Up to now there is no satisfactory explanation to this. In the present study we propose that microdosimetry will help reduce the discrepancy significantly. The ICRP Human Respiratory Tract Model (HRTM) has been applied to calculate the effective dose conversion factor. All parameters have been kept at their best estimates. Modifications were made in the calculation of the absorbed fractions of alpha particles. In contrast to the ICRP approach where the energy has been considered to be deposited in the layer containing the sensitive cells, we used a microdosimetric approach in which the alpha particles deposit their energy only in the nuclei of sensitive cells. This modification alone has lowered the dose conversion factor by about one-third (from 15 mSv/WLM down to approximately 10 mSv/ WLM). Received: 19 February 2001 / Accepted: 10 July 2001     

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 genotoxin 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. Our experiments demonstrated that the mammalian lung fibroblast/micronucleus method has the potential to (1) detect species differences in the induction of in vivo genotoxic damage in the lungs by inhaled environmentalal agents; (2) evaluate exposure-response relationships for in vivo induction of genetic damage; and (3) determine the persistence in vivo of preclastogenic and premutagenic lesions in cell populations.     

Nontypeable Haemophilus influenzae Induces Sustained Lung Oxidative Stress and Protease Expression

Nontypeable Haemophilus influenzae (NTHi) is a prevalent bacterium found in a variety of chronic respiratory diseases. The role of this bacterium in the pathogenesis of lung inflammation is not well defined. In this study we examined the effect of NTHi on two important lung inflammatory processes 1), oxidative stress and 2), protease expression. Bronchoalveolar macrophages were obtained from 121 human subjects, blood neutrophils from 15 subjects, and human-lung fibroblast and epithelial cell lines from 16 subjects. Cells were stimulated with NTHi to measure the effect on reactive oxygen species (ROS) production and extracellular trap formation. We also measured the production of the oxidant, 3-nitrotyrosine (3-NT) in the lungs of mice infected with this bacterium. NTHi induced widespread production of 3-NT in mouse lungs. This bacterium induced significantly increased ROS production in human fibroblasts, epithelial cells, macrophages and neutrophils; with the highest levels in the phagocytic cells. In human macrophages NTHi caused a sustained, extracellular production of ROS that increased over time. The production of ROS was associated with the formation of macrophage extracellular trap-like structures which co-expressed the protease metalloproteinase-12. The formation of the macrophage extracellular trap-like structures was markedly inhibited by the addition of DNase. In this study we have demonstrated that NTHi induces lung oxidative stress with macrophage extracellular trap formation and associated protease expression. DNase inhibited the formation of extracellular traps.     

Impaired neutrophil extracellular trap formation: a novel defect in the innate immune system of aged individuals

Neutrophil extracellular traps (NETs) are a recently discovered addition to the defensive armamentarium of neutrophils, assisting in the immune response against rapidly dividing bacteria. Although older adults are more susceptible to such infections, no study has examined whether aging in humans influences NET formation. We report that TNF‐α‐primed neutrophils generate significantly more NETs than unprimed neutrophils and that lipopolysaccharide (LPS)‐ and interleukin‐8 (IL‐8)‐induced NET formation exhibits a significant age‐related decline. NET formation requires generation of reactive oxygen species (ROS), and this was also reduced in neutrophils from older donors identifying a mechanism for reduced NET formation. Expression of IL‐8 receptors (CXCR1 and CXCR2) and the LPS receptor TLR4 was similar on neutrophils from young and old subjects, and neutrophils challenged with phorbol‐12‐myristate‐13‐acetate (PMA) showed no age‐associated differences in ROS or NET production. Taken together, these data suggest a defect in proximal signalling underlies the age‐related decline in NET and ROS generation. TNF‐α priming involves signalling through p38 MAP kinase, but activation kinetics were comparable in neutrophils from young and old donors. In a clinical setting, we assessed the capacity of neutrophils from young and older patients with chronic periodontitis to generate NETs in response to PMA and hypochlorous acid (HOCL). Neutrophil extracellular trap generation to HOCL, but not PMA, was lower in older periodontitis patients but not in comparison with age‐matched controls. Impaired NET formation is thus a novel defect of innate immunity in older adults but does not appear to contribute to the increased incidence of periodontitis in older adults.     

Radon sources and impacts: a review of mining and non-mining issues

Radon is a ubiquitous natural carcinogen derived from the three primordial radionuclides of the uranium series (²³⁸U and ²³⁵U) and thorium series (²³²Th). In general, it is present at very low concentrations in the outdoor or indoor environment, but a number of scenarios can give rise to significant radiological exposures. Historically, these scenarios were not recognised, and took many centuries to understand the links between the complex behaviour of radon and progeny decay and health risks such as lung cancer. However, in concert with the rapid evolution in the related sciences of nuclear physics and radiological health in the first half of the twentieth century, a more comprehensive understanding of the links between radon, its progeny and health impacts such as lung cancer has evolved. It is clear from uranium miner studies that acute occupational exposures lead to significant increases in cancer risk, but chronic or sub-chronic exposures, such as indoor residential settings, while suggestive of health risks, still entails various uncertainties. At present, prominent groups such as the BEIR or UNSCEAR committees argue that the ‘linear no threshold’ (LNT) model is the most appropriate model for radiation exposure management, based on their detailed review and analysis of uranium miner, residential, cellular or molecular studies. The LNT model implies that any additional or excess exposure to radon and progeny increases overall risks such as lung cancer. A variety of engineering approaches are available to address radon exposure problems. Where high radon scenarios are encountered, such as uranium mining, the most cost effective approach is well-engineered ventilation systems. For residential radon problems, various options can be assessed, including building design and passive or active ventilation systems. This paper presents a very broad but thorough review of radon sources, its behaviour (especially the importance of its radioactive decay progeny), common mining and non-mining scenarios which can give rise to significant radon and progeny exposures, followed by a review of associated health impacts, culminating in typical engineering approaches to reduce exposures and rehabilitate wastes.     

Interactions of nanoparticles with pulmonary structures and cellular responses

Combustion-derived and synthetic nano-sized particles (NSP) have gained considerable interest among pulmonary researchers and clinicians for two main reasons. 1) Inhalation exposure to combustion-derived NSP was associated with increased pulmonary and cardiovascular morbidity and mortality as suggested by epidemiological studies. Experimental evidence has provided a mechanistic picture of the adverse health effects associated with inhalation of combustion-derived and synthetic NSP. 2) The toxicological potential of NSP contrasts with the potential application of synthetic NSP in technological as well as medicinal settings, with the latter including the use of NSP as diagnostics or therapeutics. To shed light on this paradox, this article aims to highlight recent findings about the interaction of inhaled NSP with the structures of the respiratory tract including surfactant, alveolar macrophages, and epithelial cells. Cellular responses to NSP exposure include the generation of reactive oxygen species and the induction of an inflammatory response. Furthermore, this review places special emphasis on methodological differences between experimental studies and the caveats associated with the dose metrics and points out ways to overcome inherent methodological problems.     

Interleukin 1 stimulates hexose transport in fibroblasts by increasing the expression of glucose transporters

Exposure of quiescent cultures of human gingival fibroblasts (HuGi) and porcine synovicocytes (PSF) to human recombinant interleukin 1 alpha or -beta (IL1 alpha and -beta) enhanced the rate of glycolysis as judged by increased lactate production. The cytokines also increased uptake of [3H]2-deoxyglucose (DG) in a time- and dose-dependent manner. Stimulation of DG uptake was first evident 6-8 h following addition of IL1 and was maximal by 24-30 h. IL1 alpha and -beta were equipotent. Half-maximal stimulation occurred at approximately 1 pM IL1; maximal stimulation (2.5-4.5-fold in HuGi, 3-7-fold in PSF) was obtained with approximately 80 pM IL1. The dose-response curves for lactate production and DG uptake were similar. Increased DG uptake was blocked by specific antisera to IL1 and by inhibitors of protein and RNA synthesis but not by indomethacin, an inhibitor of prostaglandin production. DG uptake was enhanced by IL1 in serum-starved cells in the presence of neutralizing anti-platelet-derived growth factor serum. The effect was therefore not secondary to prostaglandin or platelet-derived growth factor production. No increase in cell cycling was detected in IL1-treated cells under the experimental conditions. Kinetic analysis revealed that the Vmax for DG uptake was increased by IL1 (from 36 to 144 pmol/min/mg of cell protein), whereas the Km was unchanged. HuGi cells were pulse-labeled with [35S]methionine following exposure to IL1. Cell lysates were immunoprecipitated using a specific antiserum raised against human erythrocyte glucose transporter. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis/autoradiography of these immunoprecipitates revealed dose- and time-dependent increases in the net rate of glucose transporter synthesis which mirrored the changes in DG uptake.     

Differential regulation of IL 6, IL 1 A, IL 1 beta and TNF alpha production in LPS-stimulated human monocytes: role of cyclic AMP.

Interleukin 6 (IL 6), IL 1 alpha, IL beta and tumor necrosis factor (TNF) alpha are four cytokines induced in monocytes by lipopolysaccharide (LPS); however, it is unclear whether the mechanisms which control their production are similar. In this study, we report the effects of prostaglandin E2 (PGE2), and two other cAMP-elevating agents, dibutyryl cAMP and 3-isobutyl-1-methyl-xanthine, on the in vitro LPS-induced production of IL 6, IL 1 alpha, IL 1 beta and TNF alpha by human monocytes. The production of these four cytokines was found to be selectively regulated in monocytes, by increases in intracellular cAMP levels. In effect, such agents enhanced, in a dose-dependent manner, both extracellular and cell-associated IL 6 production by LPS-stimulated monocytes. In contrast, it was confirmed, using the same samples, that these cAMP-elevating agents inhibit both extracellular and cell-associated TNF alpha production in a dose-dependent manner. IL 1 alpha and IL 1 beta production, measured by means of specific immunoreactive assays, were not significantly modified. Kinetic analysis showed that the potentiating effect of cAMP on IL 6 production, along with its inhibiting effect on TNF alpha production, could be seen as early as 1 hr after LPS stimulation. These results demonstrate that IL 6, TNF alpha, IL 1 alpha and IL 1 beta production can be differently modulated by an agent, PGE2, which is produced simultaneously by LPS-stimulated monocytes. Such differential autocrine modulation may play an important role in the regulation of the production of cytokines participating in immune and inflammatory responses.     

Differential induction of apoptosis by cigarette smoke extract in primary human lung fibroblast strains: implications for emphysema

Cigarette smoke is the principal cause of emphysema. Recent attention has focused on the loss of alveolar fibroblasts in the development of emphysema. Fibroblasts may become damaged by oxidative stress and undergo apoptosis as a result of cigarette smoke exposure. Not all smokers develop lung diseases associated with tobacco smoke, a fact that may reflect individual variation among human fibroblast strains. We hypothesize that fibroblasts from different human beings vary in their ability to undergo apoptosis after cigarette smoke exposure. This could account for emphysematous changes that occur in the lungs of some but not all smokers. Primary human lung fibroblast strains were exposed to cigarette smoke extract (CSE) and assessed for viability, morphological changes, and mitochondrial transmembrane potential as indicators of apoptosis. We also examined the generation of intracellular reactive oxygen species (ROS), 4-hydroxy-2-nonenal, and changes in glutathione (GSH) and glutathione disulfide (GSSG) levels. Each human lung fibroblast strain exhibited a differential sensitivity to CSE as judged by changes in mitochondrial membrane potential, viability, ROS generation, and glutathione production. Interestingly, the thiol antioxidants N-acetyl-L-cysteine and GSH eliminated CSE-induced changes in fibroblast morphology such as membrane blebbing, nuclear condensation, and cell size and prevented alterations in mitochondrial membrane potential and the generation of ROS. These findings support the concept that oxidative stress and apoptosis are responsible for fibroblast death associated with exposure to tobacco smoke. Variations in the sensitivity of fibroblasts to cigarette smoke may account for the fact that only some smokers develop emphysema.     

Post-receptor formation of active forms of oxygen in nonphagocytic cells]

Generation of reactive oxygen species (ROS) in A431 cells, NIH3T3 fibroblasts expressing normal epidermal growth factor (EGF) receptor, L929 fibroblasts, and in mouse peritoneal macrophages (professionally phagocytic cells) upon the effect of different activators has been studied. It has been shown that ROS formation in A431 and NIH3T3 cells upon the effect of EGF is time- and dose-dependent process. A variety of stimuli were used to stimulate macrophage ROS production. However, the effect of only phorbol ester, opsonized zymozan, peptide fMLP, and platelet activating factor led to ROS generation, whereas tumor necrosis factor alpha, interferon gamma, and lipopolysaccharide did not stimulate macrophage oxidative burst. The literature data on ROS generation in a variety of cell types are presented. ROS formed in cells acted upon certain agents are considered as the molecules participating in intracellular signaling.     

Serine proteases increase oxidative stress in lung cells

Several serine proteases are directly cytotoxic. We investigated whether the cytotoxic effects of proteases are associated with increased levels of reactive oxygen species (ROS) in cells. We found that treatment of lung fibroblasts or bronchial epithelial cells with relatively high concentrations (0.1--100 U/ml) of neutrophil elastase, trypsin, and Pronase increased ROS levels in the mitochondria and cytoplasm. The protease-induced increase in ROS was associated with oxidative cellular injury as determined by generation of 8-hydroxy-2'-deoxyguanosine and malonaldehyde plus 4-hydroxyalkenal. The protease-induced increase in ROS was not merely due to cell detachment because the proteases also caused an increase in ROS in suspended cells, which precluded attachment to the extracellular matrix. The protease-induced increase in ROS appears to contribute to cytotoxicity because cell death induced by proteases was attenuated by treatment with catalase, a decomposer of H(2)O(2), and accelerated by treatment with aminotriazole, a catalase inhibitor. These results suggest that several proteases increase oxidative stress, indicating a direct interaction between proteases and ROS in mediating cytotoxicity.     

Alpha melanocyte stimulating hormone inhibits immunostimulatory and inflammatory actions of interleukin 1

The ability of interleukin 1 (IL 1) to augment the proliferation of murine thymocytes in vitro was inhibited in a dose-dependent manner by the neuropeptide alpha-melanocyte-stimulating hormone (alpha MSH). The minimal effective concentration of alpha MSH was 10(-11) M. Maximal effect occurred between 10(-8) and 10(-7) M, with diminishing effectiveness at higher concentrations. IL 1-induced production of prostaglandin E (PGE) by fibroblasts was also inhibited by alpha MSH with a biphasic dose response. The minimal effective concentration was 10(-11) M, and maximum effect was achieved at 10(-10) M. alpha MSH appeared to affect the interaction of IL 1 with its target cells in a specific manner, because it did not inhibit basal mitogen-induced thymocyte proliferation or IL 2-induced proliferation of a cytotoxic T lymphocyte line. Furthermore, production of IL 1 by endotoxin-stimulated monocytes was not affected by alpha MSH. An analog of alpha MSH (Nle4, D-Phe7 alpha MSH), which is highly potent in other melanotropin-sensitive systems, did not affect the action of IL 1 on thymocytes, suggesting that the immunomodulatory effects of alpha MSH may not be mediated by the classic melanocyte alpha MSH receptor. The influence of alpha MSH on thymocytes and fibroblasts suggests that alpha MSH is an endogenous antagonist of IL 1, perhaps important for limiting inflammatory damage to host tissues.     

Consequences of parental exposure to epidermal growth factor for progeny cell division

The consequences of parental exposure to epidermal growth factor (EGF), for progeny cell cycle times was investigated. Slowly dividing mouse 3T3 fibroblasts were exposed to EGF for 8 hr, the EGF was withdrawn, and the cell cycle times of parental and progeny cells were measured by time-lapse video microscopy. It was observed that exposure to EGF induced a round of cell division following a lag phase of approximately 8 hr. The progeny of these cells exhibited accelerated cell cycle times compared to cells that had not been exposed to EGF. Parental cell division time was significantly correlated with progeny cell cycle time. Sibling progeny cell cycle times were also significantly correlated. EGF can therefore apparently exert an effect on the cell cycle times of more than one generation of cells.