scholarly journals Is Response to Genotoxic Stress Similar in Populations of African and European Ancestry? A Study of Dose-Response After in vitro Irradiation

2021 ◽  
Vol 12 ◽  
Author(s):  
Mamadou Soumboundou ◽  
Julien Dossou ◽  
Yossef Kalaga ◽  
Innocent Nkengurutse ◽  
Ibrahima Faye ◽  
...  
Keyword(s):  
Chromosomal Aberrations ◽  
Dose Response ◽  
Genotoxic Stress ◽  
European Ancestry ◽  
Response Curves ◽  
Blood Samples ◽  
Dicentric Chromosomes ◽  
Significant Difference ◽  
Dose Response Curves

Background: Exposure to genotoxic stress such as radiation is an important public health issue affecting a large population. The necessity of analyzing cytogenetic effects of such exposure is related to the need to estimate the associated risk. Cytogenetic biological dosimetry is based on the relationship between the absorbed dose and the frequency of scored chromosomal aberrations. The influence of confounding factors on radiation response is a topical issue. The role of ethnicity is unclear. Here, we compared the dose-response curves obtained after irradiation of circulating lymphocytes from healthy donors of African and European ancestry.Materials and Methods: Blood samples from six Africans living in Africa, five Africans living in Europe, and five Caucasians living in Europe were exposed to various doses (0–4 Gy) of X-rays at a dose-rate of 0.1 Gy/min using an X-RAD320 irradiator. A validated cohort composed of 14 healthy Africans living in three African countries was included and blood samples were irradiated using the same protocols. Blood lymphocytes were cultured for 48 h and chromosomal aberrations scored during the first mitosis by telomere and centromere staining. The distribution of dicentric chromosomes was determined and the Kruskal-Wallis test was used to compare the dose-response curves of the two populations.Results: No spontaneous dicentric chromosomes were detected in African donors, thus establishing a very low background of unstable chromosomal aberrations relative to the European population. There was a significant difference in the dose response curves between native African and European donors. At 4 Gy, African donors showed a significantly lower frequency of dicentric chromosomes (p = 8.65 10–17), centric rings (p = 4.0310–14), and resulting double-strand-breaks (DSB) (p = 1.32 10–18) than European donors. In addition, a significant difference was found between African donors living in Europe and Africans living in Africa.Conclusion: This is the first study to demonstrate the important role of ethnic and environmental factors that may epigenetically influence the response to irradiation. It will be necessary to establish country-of-origen-specific dose response curves to practice precise and adequate biological dosimetry. This work opens new perspective for the comparison of treatments based on genotoxic agents, such as irradiation.

Methacholine dose-response curves in normal and asthmatic man: Effect of starting conductance and pharmacological antagonism

1984 ◽  
Vol 66 (6) ◽  
pp. 665-673 ◽  
Author(s):  
K. F. Chung ◽  
P. D. Snashall
Keyword(s):  
Dose Response ◽  
Normal Subjects ◽  
Small Degree ◽  
Response Curves ◽  
Significant Difference ◽  
Positive Linear Correlation ◽  
Dose Response Curves ◽  
Dose Dependent Increase ◽  
Dose Dependent ◽  
Different Doses

1. The bronchial response of 11 normal and ten stable asthmatic subjects to increasing concentrations of methacholine aerosol was assessed by serial measurements of specific airways conductance (scaw) in a body plethysmograph. 2. Cumulative log dose-response curves were constructed. The threshold provocative dose of methacholine needed to cause a 35% fall in starting sCaw (pD35) and the steepest slope of the response were measured from each curve. 3. On separate days subjects were premedicated with 0.9% NaCl solution (control) in duplicate, chlorpheniramine, salbutamol and atropine, the last-named at two different doses, one twice the other. 4. Asthmatic subjects had a lower mean PD35 and a lower mean slope than normal subjects. 5. Pretreatment with salbutamol resulted in a greater increase in sGaw than after atropine but caused a smaller increase in PD35 in both groups. There was a dose-dependent increase in PD3s after the two doses of atropine, but no significant difference in bronchodilatation between doses. Mean steepest slope approximately doubled in these three sets of challenges. 6. Chlorpheniramine caused a small degree of bronchodilatation and there was a non-significant increase in mean PD3s and in mean steepest slope in both normal and asthmatic groups. 7. There was a positive linear correlation between starting sGaw and steepest slope in each group of premedicated challenges, such that when

Perception of a unilateral light stimulus

1983 ◽  
Vol 303 (1116) ◽  
pp. 479-487 ◽  
Keyword(s):  
Light Intensity ◽  
Dose Response ◽  
Light Stimulus ◽  
Biological Systems ◽  
Response Curves ◽  
Action Spectra ◽  
Potential Problems ◽  
Dose Response Curves ◽  
Lack Of Knowledge

An organism can detect light direction given a gradient in light intensity within the organism. This gradient, which may be measured temporally or spatially, can be produced by screening or by refraction. The ramifications of the method of producing the gradient are potentially great, with possible effects on the shape of dose-response curves and action spectra. Two biological systems, amoebal phototaxis in Dictyostelium and phototropism by monocot seedlings, illustrate some potential problems. In the former system, no obvious mechanism exists for producing a substantial internal gradient in light intensity. This indicates our lack of knowledge concerning the amount of gradient necessary for an organism to measure light direction. In the latter system, it is evident that a gradient in light intensity is established by screening for second positive phototropism . However, screening may not be the method used for first positive phototropism. The implications of refraction as the mechanism involved in first positive phototropism are sufficiently great to warrant a thorough examination of the role of screening and refraction in first positive phototropism.

Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo

1994 ◽  
Vol 77 (3) ◽  
pp. 1325-1332 ◽  
Author(s):  
D. Cheung ◽  
H. van der Veen ◽  
J. den Hartigh ◽  
J. H. Dijkman ◽  
P. J. Sterk
Keyword(s):  
Substance P ◽  
Dose Response ◽  
Forced Expiratory Volume ◽  
Maximal Response ◽  
Response Curves ◽  
Airway Narrowing ◽  
Dose Response Curves ◽  
High Doses

We tested the hypothesis that the inhaled tachykinin substance P (SP) can induce hyperresponsiveness to methacholine in asthmatic subjects in vivo. Nine atopic nonsmoking asthmatic males with normal forced expiratory volume in 1 s (FEV1; > 80% predicted) and increased methacholine sensitivity [provocative concn causing 20% fall in FEV1 (PC20) < 8 mg/ml] participated in a two-period placebo-controlled crossover study. Dose-response curves to SP (0.25–8 mg/ml) and placebo were recorded on 2 randomized days at least 1 wk apart, and methacholine tests were done 24 h before and 2 and 24 h after these challenges. The responses were measured by FEV1 (%fall from baseline). The position of the methacholine dose-response curves was expressed by the PC20 FEV1 and by the maximal response by the plateau level (MFEV1). SP caused a dose-dependent fall in FEV1 (P < 0.001). There was a slight increase in the PC20 FEV1 at 2 and 24 h, which was not significantly different between placebo and SP. Similarly, there was a reduction in MFEV1 at 2 h after both pretreatments. However, at 24 h after SP inhalation, MFEV1 increased compared with placebo. These changes in MFEV1 were significantly different between SP and placebo by 5.2 +/- 2.2% fall (SE) (P < 0.05). We conclude that 1) a bronchoconstrictive dose of SP, compared with placebo, enhances maximal airway narrowing to methacholine in asthma 24 h after inhalation and 2) tolerance develops to high doses of inhaled methacholine. These findings are suggestive of a role of SP in causing excessive airway narrowing in asthma by inflammatory mechanisms.

Role of alpha-adrenergic receptors in the intrinsic inotropic selectivity of dobutamine in anesthetized dogs

1985 ◽  
Vol 63 (6) ◽  
pp. 630-635 ◽  
Author(s):  
Joel E. Shaffer ◽  
Richard J. Gorczynski
Keyword(s):  
Heart Rate ◽  
Dose Response ◽  
Contractile Force ◽  
Response Curves ◽  
Alpha Adrenergic Receptors ◽  
Rate Versus ◽  
Anesthetized Dogs ◽  
Series Of Experiments ◽  
Dose Response Curves

The inotropic selectivity of dobutamine was examined in pentobarbital-anesthetized, vagotomized dogs pretreated with a ganglion blocker. The purpose was to determine if, in the presence of hexamethonium and vagotomy, the inotropic selectivity of dobutamine could be attributed to an action of dobutamine on alpha-adrenoreceptors. Dose–response curves were determined for either isoproterenol or dobutamine 30 min after treatment with hexamethonium (20 mg/kg). Analysis of heart rate versus right ventricular contractile force showed that dobutamine produced less tachycardia for a given increase in contractile force than isoproterenol; this was statistically significant when contractile force was increased by either 50 or 100%. In a separate series of experiments, dobutamine (8 μg∙kg−1∙min−1) was administered 20 min after propranolol (3 mg/kg). Under these conditions there was a slight increase in contractile force which represented 12% of the dobutamine response prior to propranolol administration. This increase in contractile force in the presence of propranolol was completely prevented by the addition of phentolamine (1 mg/kg). Consequently, in another series of experiments, dose–response curves for dobutamine were performed in the presence of hexamethonium before and 30 min after phentolamine alone (1 mg/kg) or vehicle. Phentolamine did not influence the effect of dobutamine on heart rate or contractile force, but prevented the increase in diastolic blood pressure caused by dobutamine. In addition, analysis of heart rate versus contractile force indicated that there were no statistically significant effects of phentolamine on the inotropic selectivity of dobutamine. Thus, it appears that dobutamine may exert an effect on myocardial contractility through activation of alpha-adrenoreceptors; however, this effect is so minimal that in the presence of hexamethonium and vagotomy, activation of alpha-adrenoreceptors does not appear to influence the inotropic selectivity of dobutamine.

Dose-response Curves in the Fibrin Plate Assay Fibrinolytic Activity of Proteases

1974 ◽  
Vol 32 (02/03) ◽  
pp. 356-365 ◽  
Author(s):  
F Haverkate ◽  
D. W Traas
Keyword(s):  
Dose Response ◽  
Fibrinolytic Activity ◽  
Enzyme Concentration ◽  
Response Curves ◽  
Agar Gel ◽  
Porcine Tissue ◽  
Plate Assay ◽  
Fibrin Plate ◽  
Different Types ◽  
Dose Response Curves

SummaryIn the fibrin plate assay different types of relationships between the dose of applied proteolytic enzyme and the response have been previously reported. This study was undertaken to determine whether a generally valid relationship might exist.Trypsin, chymotrypsin, papain, the plasminogen activator urokinase and all of the microbial proteases investigated, including brinase gave a linear relationship between the logarithm of the enzyme concentration and the diameter of the circular lysed zone. A similar linearity of dose-response curves has frequently been found by investigators who used enzyme plate assays with substrates different from fibrin incorporated in an agar gel. Consequently, it seems that this linearity of dose-response curves is generally valid for the fibrin plate assay as well as for other enzyme plate bioassays.Both human plasmin and porcine tissue activator of plasminogen showed deviations from linearity of semi-logarithmic dose-response curves in the fibrin plate assay.

OVARIAN ASCORBIC ACID DEPLETION TEST FOR LUTEINIZING HORMONE

1967 ◽  
Vol 56 (4) ◽  
pp. 619-625 ◽  
Author(s):  
Hans Jacob Koed ◽  
Christian Hamburger
Keyword(s):  
Ascorbic Acid ◽  
Luteinizing Hormone ◽  
Dose Response ◽  
Response Curve ◽  
Dose Response Curve ◽  
Human Origin ◽  
Response Curves ◽  
Significant Difference ◽  
The Mean ◽  
Different Levels

ABSTRACT Comparison of the dose-response curves for LH of ovine origin (NIH-LH-S8) and of human origin (IRP-HMG-2) using the OAAD test showed a small, though statistically significant difference, the dose-response curve for LH of human origin being a little flatter. Two standard curves for ovine LH obtained with 14 months' interval, were parallel but at different levels of ovarian ascorbic acid. When the mean ascorbic acid depletions were calculated as percentages of the control levels, the two curves for NIH-LH-S8 were identical. The use of standards of human origin in the OAAD test for LH activity of human preparations is recommended.

BIOASSAY OF THYROID HORMONE USING HYPOTHYROID TADPOLES

1962 ◽  
Vol 41 (1) ◽  
pp. 143-153 ◽  
Author(s):  
U. Henriques
Keyword(s):  
Thyroid Hormone ◽  
Dose Response ◽  
Developmental Rate ◽  
Response Curves ◽  
Sodium Salts ◽  
Dose Response Curves

ABSTRACT A bioassay of thyroid hormone has been developed using Xenopus larvae made hypothyroid by the administration of thiourea. Only tadpoles of uniform developmental rate were used. Thiourea was given just before the metamorphotic climax in concentrations that produced neoteni in an early metamorphotic stage. During maintained thiourea neotoni, 1-thyroxine and 1-triiodothyronine were added as sodium salts to the water for three days and at the end of one week the stage of metamorphosis produced was determined. In this way identical dose-response curves were obtained for the two compounds. No qualitative differences between their effects were noted except that triiodothyronine seemed more toxic than thyroxine in equivalent doses. Triiodothyronine was found to be 7–12 times as active as thyroxine.

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