• Journal of Environmental Health Sciences
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• v.50 no.4
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• pp.229-236
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• 2024

The linear no-threshold (LNT) model is an assumption that explains the dose-response relationship for health risks, allowing for linear extrapolation from high doses to low doses without a threshold. The selection of an appropriate model for low-dose risk evaluation is a critical component in the risk assessment process for hazardous agents. This paper reviews the LNT model in light of epidemiological evidence from major international consortia studying ionizing radiation. From a scientific perspective, substantial evidence supporting the LNT model has been observed in epidemiological studies of low-dose ionizing radiation exposure, although some findings suggest non-linear dose relationships for certain cancer sites and variations across populations. From a practical standpoint, the LNT remains the most useful model for radiation protection purposes, with no alternative dose-response relationship proving more appropriate. It is important to note that the LNT model does not directly reflect the magnitude of risk at the population level, and this distinction should be clearly communicated to the public. While applying the LNT model as the principal basis for radiation protection, continuous research into various dose-response relationships is crucial for advancing our understanding.

• Journal of Radiation Protection and Research
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• v.34 no.3
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• pp.102-106
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• 2009

We exposed ICR mice to low-dose (0.2 Gy) and low-dose-rate (0.7 mGy/h) $\gamma$-radiation ($^{137}Cs$) in the Low-dose-rate Irradiation Facility at the Radiation Health Research Institute to evaluate systemic effects of low-dose radiation. We compared the body and organ weights, number of blood cells (white and red blood cells and platelets), levels of biochemical markers in serum, and frequency of micronuclei in polychromatic erythrocytes between low-dose irradiated and non-irradiated control mice. The ICR mice irradiated with total doses of 0.2 and 2 Gy showed no changes in body and organ weights, number of blood cells (white and red blood cells), or frequency of micronuclei in the polychromatic erythrocytes of peripheral blood. However, the number of platelets (P = 0.002) and the liver weight (P < 0.01) were significantly increased in mice exposed to 0.2 and 2 Gy, respectively. These results suggest that a low-dose-rate of 0.7 mGy/h does not induce systemic damage. This dose promotes hematopoiesis in the bone marrow microenvironment and the proliferation of liver cells. In the future, the molecular biological effects of lower doses and dose rates need to be evaluated.

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.3
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• pp.1119-1122
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• 2016

Background: Punica granatum (PG) has been demonstrated to possess antitumor effects on various types of cancer cells. In this study, we determined antiproliferative properties of a seed extract of PG (PSE) from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate seeds was prepared. Total phenolic content (TPC) and total flavonoid content (TFC) were assessed by colorimetric assays. Antioxidant activity was determined with reference to DPPH radical scavenging activity. The cytotoxicity of different doses of PSE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell carcinoma), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer cells), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison to negative controls at all tested doses ($5-1000{\mu}g/ml$). In all studied cancer cells, PSE reduced the cell viability to values below 23%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, SKOV3 ovarian cancer cells were the most responsive to antiproliferative effects of PSE with a maximum mean growth inhibition of 86.8% vs. 82.8%, 81.4% and 80.0% in MCF-7, PC-3 and A549 cells, respectively. Conclusions: Low doses of PSE exert potent antiproliferative effects on different human cancer cells SKOV3 ovarian cancer cells as most and A549 cells ar least responsive regarding cytotoxic effects. However, the mechanisms of action need to be addressed.

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.14
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• pp.5697-5701
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• 2015

Background: Medicinal plants, especially examples rich in polyphenolic compounds, have been suggested to be chemopreventive on account of antioxidative properties. Punica granatum (PG) (pomegranate) is a well known fruit in this context, but its cytotoxicity in cancer cells has not been extensively studied. Here, we investigated the antiproliferative properties of a peel extract of PG from Iran in different human cancer cells. Materials and Methods: A methanolic extract of pomegranate peel (PPE) was prepared. Total phenolic content(TPC) and total flavonoid conetnt (TFC) were determined by colorimetric assays. Antioxidant activity was determined by DPPH radical scavenging activity. The cytotoxicity of different doses of PPE (0, 5, 20, 100, 250, 500, $1000{\mu}g/ml$) was evaluated by MTT assays with A549 (lung non small cell cancer), MCF-7 (breast adenocarcinoma), SKOV3 (ovarian cancer), and PC-3 (prostate adenocarcinoma) cells. Results: Significant (P<0.01) or very significant (P<0.0001) differences were observed in comparison with negative controls at all tested doses (5-$1000{\mu}g/ml$). In all studied cancer cells, PPE reduced the cell viability to values below 40%, even at the lowest doses. In all cases, IC50 was determined at doses below $5{\mu}g/ml$. In this regard, MCF-7 breast adenocarcinoma cells were the most responsive cells to antiprolifreative effects of PPE with a maximum mean growth inhibition of 81.0% vs. 69.4%, 79.3% and 77.5% in SKOV3, PC-3 and A549 cells, respectively. Conclusions: Low doses of PPE exert potent anti-proliferative effects in different human cancer cells and it seems that MCF-7 breast adenocarcinoma cells are the most cells and SKOV3 ovarian cancer cells the least responsive in this regard. However, the mechanisms of action need to be addressed.

• Korean Journal of Biological Psychiatry
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• v.4 no.2
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• pp.198-210
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• 1997

To examine the double-faced thymoleptic(antidepressant and antimanic) effects of risperidone in mood disorders, this article reviews the psychotropic-induced mania, thymoleptic effects of antipsychotics, therapeutic effects of risperidone and risperidone(RIS)-induced mania(RIM) in mood disorders, risk factors of RIM, possible neurochemical mechanism of these thymoleptic effects, pathophysiological and clinical significance of thymoleptic effects, and suggestive clinical guideline of RIS in mood disorders. RIS appeared effective for bipolar disorder at a lower dose than that recommended for schizophrenia, especially in the cases of maintenance of mood stabilizers, and gradual titration from low doses. Manic induction/exacerbation can occur by chance during RIS treatment in mood disorders, schizoaffective disorders, and schizophrenias. The possible risk factors for RIM are refractory mood disorder, especially in bipolar I disorder with poor initial response ; refractory schizoaffective disorders, especially in bipolar type with poor initial response ; refractory chronic schizophrenias, especially with initial responses ; psychotic features ; higher initial doses ; rapid titration ; combined therapy with antidepressants in refractory depression ; and RIS monotherapy in mania/hypomania. RIS is a drug that preferentially block 5-HT2 receptors. The effects of low dose are due mainly to the blockade of 5-HT2 receptors. There are more gradual increase in D2 blockade with increasing dose and this D2 blocking properties become apparent at higher doses. This may be related to a modulation of dopaminergic transmission by 5-HT2 antagonism at lower doses with the direct action of RIS on DA receptors coming into play at higher dose. The serotonergic antagonistic effect may be important for its effects on depressive symptoms. This, together with adequate blo-ckade of D2 receptors, may not necessarily lead to destabilization of mood disorder, but rather to more therapeutic effects. Therefore, this dose-receptor affinity relationship with both antidepressant and antimanic effects according to treatment duration can explain a continuum of antidepressant effect, antimanic effect, behavioral stimulation, and manic/hypomanic induction/exacerbation. It was the recognition of a useful psychiatric side effects by a thoughtful observer with fertile minds that led to their ultimate utilization as psychotropic drugs, i.e., phenothiazine, MAOI, TCA, and lithium. And, in vivo pharmacological challenge by novel psychotropics, as a neurochemical probe, with more specific actions is a useful tool to select pharmacologically homogeneous subgroup of the same phenotypical(clinical) condition, to further study the unknown underlying pathogenesis of various mental illnesses. Finally, RIS may be a useful alternative or adjunctive drug for patients with mood disorders without psychotic features or refractory to treatment with standard antipsychotic drugs. The more conservative doses(tirated slowly from 1-3 mg/d) of RIS, and maintenance of mood stabilizer in the cases with risk factors of RIM are recommended in mood disorder.

• Food Science of Animal Resources
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• v.28 no.3
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• pp.289-294
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• 2008

The influence of gamma irradiation with low doses (0.5, 1.0, and 1.5 kGy) on the meat quality of chicken breast was determined for 6 days of storage at $4^{\circ}C$. The pH of irradiated chicken was lower than that of the control at day 1 (p<0.05), while no difference was found among irradiation at different doses. Drip loss was higher in irradiated chicken with doses of 0.5 and 1.0 kGy compared to the control at day 1 and day 3 (p<0.05). Lightness (L) at day 1 and day 6 was increased due to irradiation (p<0.05). Redness (a) increased with irradiation doses of 1.0 and 1.5 kGy at day 1 and day 3 (p<0.05). However, no significant differences were found in yellowness (b). The number of aerobic plate count of irradiated chicken during storage was significantly lower than the control (p<0.05). E. coli and coliforms were not detected after irradiation at any dose. Also, irradiation doses of 1.0 and 1.5 kGy significantly reduced volatile basic nitrogen (VBN) and 2-thiobarbituric acid reactive substances (TBARS) values compared to the control during storage (p<0.05). These results suggest that low dose gamma irradiation can be useful to extend the shelf life of chicken breast during cold storage.

• Environmental Mutagens and Carcinogens
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• v.21 no.2
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• pp.142-148
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• 2001

We studied adaptive response in CHL cells by benzidine dihydrochloride, a derivative of benzidine, which was a major mutagenic agent in dye industry. Chromosome aberration analysis was used for the identification of adaptive response to this mutagen. Adaptive and reactive doses were confirmed by cell proliferation rate curve. Cell proliferation rate curve was obtained from the mitotic indices of cells treated with various concentrations of benzidine dihydrochloride for 24 hours. Marked adaptive responses to benzidine dihydrochloride in the induction of chromosome aberration were observed in CHL cells by pre-treatment with low concentrations of benzidine dihydrochloride (0.0047 mg/$m\ell$ or 0.0094 mg/$m\ell$) for 24 hours following post-treatment with high concentrations (0.0187, 0.0375, 0.075, 0.15 mg/$m\ell$) for 24 hours. These adaptive responses were found mostly in the type of chromatid breaks and chromatid exchanges. There is no difference in these results between two adaptive doses, 0.0047 mg/$m\ell$ and 0.0094 mg/$m\ell$. The amount of adaptive response, however, was dependent on post-treatment doses.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.390-401
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• 1997

In order to investigate the pharmacological properties of New Woohwangchungsimwon Liquid (NCL), effects of Woohwangchungsimwon Liquid (CL) and NCL were compared. In isolated rat aorta, NCL and CL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) without regard to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxation of NCL and CL. NCL and CL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NCL and CL significantly decreased heart rate. NCL and CL, at high doses, had a negative inotropic effect that was a decrease of LVDP and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NCL and CL had no effects on parameters of action potential at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NCL and CL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between two preparations.

• Development and Reproduction
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• v.18 no.4
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• pp.225-231
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• 2014

Autophagy is a homeostatic degradation process that is involved in tumor development and normal development. Autophagy is induced in cancer cells in response to chemotherapeutic agents, and inhibition of autophagy results in enhanced cancer cell death or survival. Chloroquine (CQ), an anti-malarial drug, is a lysosomotropic agent and is currently used as a potential anticancer agent as well as an autophagy inhibitor. Here, we evaluate the characteristics of these dual activities of CQ using human colorectal cancer cell line HCT15. The results show that CQ inhibited cell viability in dose- and time-dependent manner in the range between 20 to 80 uM, while CQ did not show any antiproliferative activity at 5 and 10 uM. Cotreatment of CQ with antitumor agent NVP-BEZ235, a dual inhibitor of PI3K/mTOR, rescued the cell viability at low concentrations meaning that CQ acted as an autophagy inhibitor, but CQ induced the lethal effect at high concentrations. Acridine orange staining revealed that CQ at high doses induced lysosomal membrane permeabilization (LMP). High doses of CQ produced cellular reactive oxygen species (ROS) and cotreatment of antioxidants, such as NAC and trolox, with high doses of CQ rescued the cell viability. These results suggest that CQ may exert its dual activities, as autophagy inhibitor or LMP inducer, in concentration-dependent manner.

• Biomolecules & Therapeutics
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• v.7 no.1
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• pp.66-78
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• 1999

In order to investigate the pharmacological properties of New Wonbang Woohwangchungsimwon Liquid (NSCL), effects of Wonbang Woohwangchungsimwon Liquid (SCL) and NSCL were compared. In isolated rat aorta, NSCL and SCL showed the relaxation of blood vessels in maximum contractile response to phenylephrine (10$^{-6}$ M) regardless to intact endothelium or denuded rings of the rat aorta. Furthermore, the presences of the inhibitor of NO synthase and guanylate cyclase did not affect the relaxing effect of NSCL and SCL. NSCL and SCL inhibited the vascular contractions induced by acetylcholine, prostaglandin endoperoxide or peroxide in a dose-dependent manner. In conscious spontaneously hypertensive rats (SHRs), NSCL and SCL significantly decreased heart rate. NSCL and SCL, at high doses, had a negative inotropic effect that was a decrease of left ventricular developed pressure and (-dp/dt)/(+dp/dt) in the isolated perfused rat hearts, and also decreased the contractile force and heart rate in the isolated rat right atria. In excised guinea-pig papillary muscle, NSCL and SCL had no effects on parameters of action potential such as resting membrane potential, action potential amplitude, APD$_{90}$ and V$_{max}$ at low doses, whereas inhibited the cardiac contractility at high doses. These results suggested that NSCL and SCL have weak cardiovascular effects with relaxation of blood vessels and decrease of heart rate, and that this effect is no significant differences between cardiovascular effects of two preparations.s.