Estimation of mutation rates induced by large doses of gamma, proton and neutron irradiation of the X-chromosome of the nematode Panagrellus redivivus

The radiation-resistant free-living nematode Panagrellus redivivus was used to study mutation rates in oocytes, following gamma, proton and neutron irradiation in the dose range 45-225 grays. gamma-Radiation produced approximately 0.001 lethal X-chromosomes per gray over the range tested. Proton or neutron irradiation produced approximately 0.003 lethal X-chromosomes per gray at lower doses, with the mutation rate dropping to 0.001 lethal X-chromosome per gray at the higher doses. These results suggest a dose-dependent mutation-repair system. Cell lethality was also examined. gamma-Radiation produced the greatest amount of cell lethality at all doses, while neutron irradiation had no cell lethal effect at any of the doses examined.     

Trichinella spiralis: quantitative relationships between intestinal worm burden, worm rejection, and the measurement of intestinal immunity in inbred mice

The effect of widely different doses of Trichinella spiralis muscle larvae on time to rejection of intestinal adults and on host survival was assessed in mice of the three rejection phenotypes; strong, intermediate, and weak. Rejection is weak with doses of less than 50 larvae per mouse. At these doses all mice rejected worms at a similar rate and no phenotypic variation was evident among strains. In contrast, rejection time was shortest for all strains and phenotypic variation among strains was evident in the range 50-100 muscle larvae/mouse. Above this dose the time taken to rejection increases monotonically with dose for all mouse strains examined. Despite this, the relative strength of rejection (i.e., phenotype) of a given strain of mouse was not changed at higher doses. Based on an end point of 98% rejection of the infective dose, time to rejection was predictable to +/- 1 day for all mouse strains and doses tested over the range 100-1000 worms administered. The principal reason for the increased time to complete rejection with larger worm doses was a delay in the initiation of intestinal rejection. This delay was evident above a dose of 50-100 larvae per mouse and occurred in all strains. Once begun, rejection was faster and eliminated more worms in unit time at higher doses (400-800 more) than at lower doses of worms. This appeared to be due to a stronger immune response of the host at higher doses. However, the increase in the rate of rejection was still not as great as the increase in the dose. We postulate that the delay in rejection with increased dose is due to a requirement for a "critical mass" of effectors/worm required to cause rejection. As dose increases, more time is required to reach the level at which worm rejection commences. Deaths due to higher doses of worms also occurred in a strain-specific manner and were temporally biphasic. The intestinal phase of infection produced mortality from 1 to 5 days after infection and the strongest rejection phenotype (NFS) was also the most resistant to intestinal deaths. Deaths occurring after Day 5 were due to the parenterally migrating newborn larvae. The weakest rejection phenotype, that of the B10 congenics, was also the least resistant to intestinal deaths. An experimental formula describing 98% worm rejection time with different doses was derived from the data.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effect of cyclosporin-A, antimalarial drug, on lymphocyte proliferation of Balb/c mice in vitro

Cyclosporin-A(CsA) caused inhibition of lymphocyte proliferation at higher doses (5 and 10 micrograms/ml) compared to controls. When spleen cells were preincubated with high doses of CsA and washed, the normal lymphocyte response to stimulation with mitogen (concanavalin-A) and lymphokine (interleukin-2) was not affected. The results indicate that CsA's suppressive effect at higher doses, was a temporary one and potential use of CsA to control parasitic infections should be examined.     

Features of action of low doses of gamma-radiation on yeast cells

Lethal effect of low doses and adaptive response to low doses of prolonged irradiation were investigated in experiments on yeast cells. The phenomenon of hypersensitivity at low dozes was not found in yeast cells at gamma-irradiation. The adaptive response was observed after exposure to low doses of prolonged irradiation, the degree of the reaction depends on a dose rate. The adaptive reaction was kept for some time after the termination of adaptive irradiation then the sensitivity of cells increased even in comparison with unirradiated ones.     

Modulation of short term and long term memory by steroid sexual hormones

Many studies have evidenced a functional interrelation between the nervous and endocrine systems in the modulation of mnemonic processes, and others have established the role played by certain hormones in these processes; however, few studies have dealt with the effects of sexual steroids on learning and memory. The aim of this work was to determine whether shortterm and long-term memory is subject to hormonal modulation. Male Wistar rats, randomly assigned to 13 groups, 1 control and 12 experimental groups, were trained on a one-trial passive avoidance conditioning. The control group received saline solution, and each of the 12 experimental groups received a treatment consisted in one of following pharmacological doses of: 5, 10, 20, 30 mg of testosterone enanthate, 0.2, 0.4, 0.8, 1.2 mg estradiol valeriate, or 1, 2, 4, 6 mg norandrostenolone decanoate, respectively. All substances were applied 45 min before the training session. Retention of the learned response was tested 10 min (short-term memory) and 24 h (longterm memory) after the training session. Results indicate that under these experimental conditions the short-term memory is facilitated with testosterone enanthate at doses of 20 and 30 mg, the estradiol valeriate at doses of 0.4 mg and the nor-androstenolone decanoate at doses of 4 mg, whereas the long-term memory is facilitated with testosterone enanthate at doses of 30 mg, estradiol valeriate at doses of 1.2 mg and the nor-androstenolone decanoate at doses of 4 mg. The other studied doses were no effective.     

INSECTICIDAL AND OXIDATIVE EFFECTS OF AZADIRACHTIN ON THE MODEL ORGANISM Galleria mellonella L. (LEPIDOPTERA: PYRALIDAE)

The insecticidal effects, specifically, changes in hemolymph total protein and malondialdehyde (MDA) levels, and antioxidant enzyme activities of azadirachtin (AZA) given to the wax moth, Galleria mellonella L. (Lepidoptera: Pyralidae) larvae via force feeding were investigated. Bioassays showed that the LD₅₀ and LD₉₉ (lethal dose) values of AZA were 2.1 and 4.6 μg/larva, respectively. Experimental analyses were performed with five doses of AZA (0.5, 1, 1.5, 2, and 3 μg/larva). Total protein level in larval hemolymph increased at all AZA doses at 24 h whereas a considerable decrease was observed at 2 and 3 μg/larva doses, and only an increase displayed at 1.5 μg/larva at 72 h. The level of MDA increased at 2 and 3 μg/larva doses at 24 h compared with controls. This trend was also observed at 1.5, 2, and 3 μg/larva doses at 72 h and MDA levels were lower when compared with those of 24 h at all doses except for 1.5 μg/larva dose. Catalase activity decreased at 1, 1.5, and 2 μg/larva doses at 24 h whereas increased at all doses except for 0.5 μg/larva at 72 h compared with controls. AZA led to a decline in superoxide dismutase activity at all experimental doses at 24 and 72 h except for 3 μg/larva doses at 72 h. An increase in glutathione‐S‐transferase (GST) activity was evident at all AZA doses at 24 h. AZA displayed 68% decline in GST activity at 72 h post treatments when compared to 24 h. Consequently, We infer that the toxicity of AZA extends beyond its known actions in molting processes to redox homeostasis.     

Mechanism of reduced binding capacity of plasma corticosteroid-binding globulin in acute radiation sickness

Injection of various doses of thyroxin to rats was shown to increase a binding capacity of corticosteroid-binding globulin (CSG) of blood plasma after irradiation with doses of 650 and 800 R. The effect of thyroxin was most pronounced at a mid-lethal dose of 650 R and at the early stage of radiation sickness.     

Enhanced mutagenic response of MNU by post-treatment with methylmercury,caffeine or thymidine in V79 Chinese hamster cells

Post-treatment with a non-toxic dose of thymidine, caffeine or methylmercury-hydroxide enhanced the mutagenic response from MNU at high doses, whereas no enhancement was observed with low doses of MNU. No mutagenic effects were found with thymidine, caffeine or methylmercury alone at the doses used. Quantitatively, the modifying effects observed were similar for the 3 agents which indicates the possibility of a similar way of action.     

Transformation of C3H 10T1/2 cells with 4.3 MeV alpha particles at low doses: effects of single and fractionated doses.

Oncogenic transformation of C3H 10T1/2 cells was determined after exposure to graded doses of 4.3-MeV alpha particles LET = 101 keV/microns. The source of alpha particles was 244Cm and the irradiation was done in an irradiation chamber built for the purpose. Graded doses in the range of 0.2 to 300 cGy were studied with special emphasis on the low-dose region, with as many as seven points in the interval up to 10 cGy. The dose-effect relationship was a complex function. Transformation frequency increased with dose up to 2 cGy; it seemed to flatten at doses between 2 and 20 cGy but increased again at higher doses. A total of 21 cGy was delivered in a single dose or in 3 or 10 equal fractions at an interval of 1.5 h. An inverse dose-protraction effect of 1.4 was found with both fractionation schemes. Measurements of the mitotic index of the population immediately before the various fractions revealed a strong effect on the rate of cell division even after very low doses of radiation. Mitotic yield decreased markedly with the total dose delivered, and it was as low as 50% of the control value after 4.2 cGy and 20% after 14 cGy with both fractionation schemes.     

Metabolism of D(-)lactic acid in rats given high intragastral doses

In rats given D[u-14C]-labelled DL-lactate with 3.8-13.4 mmol D-lactate per kg 0.75 by stomach tube, the exhalation of CO2 produced from and the renal excretion of D-lactate and metabolites were measured. Exhalation of D-lactate-C accounted for 45-30% of the dosage given with a decreasing proportion at higher doses. The renal excretion of D-lactate averaged 0.9% and that of metabolites from D-lactate 2.4% of the doses given. The fraction of unrecovered D-lactate accounted for about 54-68% of the doses given and increased with doses. The time course of D-lactate oxidation indicated a maximum rate of about 1.5 mmol C per kg 0.75 in 1 hr which was reached at 1 hr after infusion at the earliest and extended up to 8 hr if high doses were given.     

Irradiation of Anastrepha obliqua (Diptera: Tephritidae) revisited: optimizing sterility induction

The effects of irradiation doses increasing from 0 to 100 Gy (1 Gy is energy absorbed in J kg(-1) of irradiated material) on fertility, flight ability, survival, and sterile male mating performance were evaluated for mass-reared Anastrepha obliqua (Macquart). High sterility values (> 98.2%) for irradiated males were obtained for doses as low as 25 Gy. Egg hatch was inhibited for irradiated males crossed with irradiated females at a low dose of 20 Gy. However, we estimated that to achieve 99.9% sterility (standard goal of many sterile insect technique programs), irradiation doses had to be increased to a dose between 50 and 75 Gy. At doses of 25 Gy and greater, we observed a decreasing trend in adult flight ability and an increasing trend in adult mortality. Such differences were greater for pupae irradiated at a young age compared those irradiated 24 h before emergence. Our single most relevant finding was that sterility induction (i.e., oviposition of nonfertilized eggs) was two times greater for males irradiated at low doses (40 Gy) than for males irradiated at high doses (80 Gy) when used at a 3:1:1 sterilized male to fertile male to fertile female ratio. Males irradiated at high doses may have been outcompeted by unirradiated males when courting unirradiated females. Implications of our findings for sterile insect technique programs are discussed.     

The effect of lecirelin (GnRH) dosage on the reproductive performance of nulliparous and lactating rabbit does

The present study attempted to evaluate the effect of different doses of lecirelin intramuscularly administered at the moment of insemination on parameters such as the conception rate, the total number of rabbits per litter, the number of stillborns per litter and the abortion rate in nulliparous and lactating crossbred rabbit does. The experiment was performed with 295 crossbred female rabbits Hyplus strain PS 19 that were housed in a rabbit farm. Six days before insemination, the light-dark cycles were as follows: 16-h light (70 lx and more):8-h dark, and all does were subcutaneously injected with 25 IU of eCG 48 h before insemination. The doses of lecirelin were as follows: 0.05, 0.1, 0.2, 0.3, 0.5, 1.0, 1.5, 2.0, 2.5, 3.0, and 4.0 microg/doe, and were tested in both nulliparous and lactating female does; the doses were applied at the moment of insemination. The conception rate in nulliparous does ranged significantly from 10.0% (0.05 microg) to 89.5% (1.5 microg). The conception rate in lactating does was the lowest at a dose of 0.05 microg (10.0%), as compared with the doses starting from 0.3 microg, and was confirmed statistically significant. The lowest number of rabbits per litter was found at a lecirelin dose of 0.1 microg (6.64). This finding was statistically significant, as compared with doses equal to or exceeding 0.3 microg. No statistical differences were found for doses ranging from 0.3 to 4.0 microg in nulliparous does (9.06 versus 10.29, respectively). The lowest number of rabbits per litter in lactating does was found at a dose of 0.05 microg (8.28) while the highest number of rabbits was detected at a dose of 4.0 microg (10.73), without statistically significant differences among individual doses. Generally, the number of rabbits per litter in lactating rabbit does was higher than that in nulliparous does (P<0.05). One negative finding is that abortions occurred in lactating does at the intramuscular application of a dose equal to or exceeding 1.5 microg, and in nulliparous does at a dose equal to or exceeding 2.0 microg.     

Characteristic cytogenetic effects of small doses of ionizing radiation

A study was made of the frequency of chromosome aberrations in human lymphocyte culture after gamma-irradiation (60Co) with doses ranging from 0.05 to 1.0 Gy at dose--rates of 0,005, 0.05 and 0.5 Gy/min. The frequency of structural changes in chromosomes at low doses was higher than it was expected in the case of extrapolating the effect produced by high to low doses of radiation; within the dose range from 0.1 to 0.5 Gy a plateau was registered for aberrations of the exchange type (dicentrics and rings). The abnormal character of the dose dependence of the yield of chromosome aberrations persisted with all three dose - rates under study.     

UVB irradiation-induced impairment of keratinocytes and adaptive responses to oxidative stress

UVB irradiation of human skin is known to induce pathophysiological processes as oxidative stress and inflammation. HaCaT keratinocytes represent a well-established in vitro model system to investigate the influence of UVB irradiation on cell cultures. It was the aim of these investigations to study the effects of moderate UVB doses on cellular and mitochondrial integrity of HaCaT keratinocytes, biomarkers of oxidative stress and antioxidant protection by superoxide dismutases. F₂-isoprostane concentrations were UVB dose-dependently enhanced reaching a plateau at 50 mJ/cm². Cell viability was reduced and apoptosis was enhanced with increasing UVB doses. The activities of the respiratory chain complexes were practically not altered at lower UVB doses, up to 50 mJ/cm², whereas remarkable decreases, also for the levels of cardiolipin species, were seen at 100 mJ/cm². As an adaptive response to the enhanced oxidative stress, protein levels of MnSOD increased about 3-fold at 50 mJ/cm² and decreased at higher doses. From the data it can be concluded that keratinocytes are sufficiently protected at low UVB doses, whereas higher doses lead to irreversible cell damage.     

Effect of gamma radiation on the immunobiological and immunochemical properties of cholera exotoxin. I. Change in the biological activity of nonpurified cholera exotoxin as affected by ionizing radiation

Crude cholera exotoxin (filtrate toxin) was irradiated with increasing doses of gamma radiation. A significant drop in enterotoxicity, in the activity of the permeation factor and a decrease in toxicity were shown to occur as radiation doses increased. Radiation doses of 50-70 kGy were found to completely inactivate enterotoxicity in liquid toxic preparations. A higher radioresistance of dried preparations in comparison with liquid ones was registered: inactivation occurred at 150-200 kGy. Different batches of the initial filtrate toxin had varying radiosensitivity. The sterilizing effect of gamma radiation was achieved at doses of 20 kGy for liquid preparations and 30 kGy for dried preparations. During the prolonged storage of the irradiated preparations of crude toxin (the term of observation being 1.5 years) at different temperatures no reversion of toxicity was found to occur, while their immunogenic properties remained unchanged.     

The dose-response relationship at very low doses of acrylamide is linear in the flow cytometer-based mouse micronucleus assay

Acrylamide (AA) is genotoxic and has been classified as a probable human carcinogen. Human exposure to AA may be high by the consumption of starch-based food that has been treated at high temperature, e.g. potato chips and crisps. For risk assessment, extrapolation to the expected low doses to humans will be more reliable when data from low experimental doses can be used. We have registered the effects of a series of low doses in the sensitive flow cytometer-based micronucleus assay in mice, paying special attention to deviations from the expected linear dose-response function. Two experiments were performed with CBA mice, injected i.p. with different doses of AA. In one experiment the effects of 22 doses (two mice per dose) ranging from 0 to 100 mg/kg b.w. were studied. In the second experiment seven doses (five mice per dose) ranging from 0 to 30 mg/kg b.w. were used. In both experiments, a clear increase of the frequency of micronucleated erythrocytes was seen, already at the lowest doses used. The dose-response function was found to be linear with a tendency to have a steeper rise at the lowest doses. The low DNA content of the micronuclei indicated an absence of whole chromosomes, i.e. no aneugenic effect of AA.     

In situ structural analysis of microsomal UDP-glucuronyltransferases by radiation inactivation

The structure of the UDP-glucuronyltransferases in microsomes from guinea pig and rat liver was examined in situ by radiation inactivation analysis. The p-nitrophenol conjugating activity of guinea pig microsomes increased at lower doses of radiation; at higher doses (greater than or equal to 36 megarads), activity showed a first order decline yielding a target size of 71 +/- 9 kDa. Treating microsomes with Triton X-100 eliminated the activation seen at lower doses of radiation and yielded a simple exponential decrease in activity which gave a larger target size (95 +/- 18 kDa). A monoexponential decrease in activity was seen in sonicated microsomes, at greater than or equal to 36 megarads. The same response was obtained when the reaction was assayed in the reverse direction. The estrone conjugating activity of guinea pig microsomes was similarly activated at lower doses of radiation and declined at higher doses (greater than or equal to 36 megarads), with a target size of 57 +/- 11 kDa. Allosteric activation of the enzyme by UDP-N-acetylglucosamine was eliminated by lower doses of radiation. Thus, activation of the enzyme by radiation, detergent, sonication, and UDP-N-acetylglucosamine appear to be interdependent. These activations are postulated to be due to the existence of the enzyme in an oligomeric form which can be dissociated into monomers with higher activity. The same biphasic activation-inactivation curves were obtained for p-nitrophenol conjugation in rat liver microsomes. The target sizes were 54 +/- 8 kDa (p-nitrophenol in the forward direction) and 66 +/- 10 kDa (p-nitrophenol in the reverse direction). Thus, the enzyme appears to be smaller in rat liver as compared with guinea pig liver. Lithocholate glucuronidating activity in rat liver microsomes (at greater than 36 megarads) gave a target size of 74 +/- 1 kDa.     

Effects of oral estrone on rat energy balance

Oral doses of estrone from 10 nmol/(kg day) to 10 micromol/(kg day) were given to adult Wistar male rats for 10 days. Body composition, energy balance, total body estrone balance and plasma metabolites and hormones were measured at the end of the treatment. Body weight (as well as food intake, body energy, fat and water accrual) increased at doses in the 10--100 nmol/(kg day) range, but decreased at higher doses. Energy expenditure decreased with increasing doses of estrone. Plasma metabolite changes suggested the maintenance of energy homeostasis, and lipid parameters indicated that lipid mobilization increased with the increasing doses of estrone. Plasma estrone, acyl-estrone and estradiol levels decreased at low doses and increased at high doses of estrone. We conclude that: (a) repeated estrone gavages, even at very high doses, do not result in the accrual of estrone in the body; (b) low doses of estrone promote growth and high doses decrease body mass and fat accretion; (c) administration of estrone at low doses decreases its circulating levels and the levels of estradiol and acyl-estrone, a situation reverted at higher doses and (d) estrone administration induces a dose-dependent shift towards lower energy expenditure.     

Effect of Bavistin,Cotoran and Curacron on Egyptian soil fungi

Tests were conducted to determine the effects of the fungicide Bavistin (Carbendazim), the herbicide Cotoran (Fluometuron) and the insecticide Curacron on Egyptian soil fungi when applied at the recommended field dose, and four and eightfold field doses. Bavistin when added to the soil induced a regular significant inhibition of the total count of fungi by the 3 doses after 5 and 40 days and by the higher doses after 80 days. The response ofAspergillus to this fungicide was almost similar to that of the total count. Cotoran was of no significant effect on the total count of fungi after 2 days at all doses, but after 5 days the herbicide was significantly depressive at the medium and the high doses. After 80 days the effect changed into significant promotion at the field dose only. Curacron was significantly toxic to the total count of soil fungi, after the shorter and longer periods at the 3 doses.