Comparative incidence of reticuloendothelial tumors in C57BL mice after exposure to tritiated water

A total of 2,377 C 57 Bl/6M mice were assigned to control groups and experimental groups exposed to tritiated water administered as a pulse injection or in drinking water, at a dose of 1.0 microCi per injection or per ml of drinking water. Weanlings were observed for the duration of life span. Data analysis was based on two coefficient estimates (1) individual carcinogenic induction coefficient and (2) specific tumorigenic induction coefficient. The carcinogenic potency of tritium was found to be dual in nature in enhancing the absolute induction of lymphocytic lymphomas in both sexes as well as their relative induction in competition with reticulo-endothelial tumors of other types.     

Radioprotection by caffeine pre- and post-treatment in the bone marrow chromosomes of mice given whole-body gamma-irradiation.

The effect of caffeine given as pre- and post-treatment in mice exposed to whole-body gamma-irradiation (1.5 Gy 60Co gamma-rays) was studied. The pre-treatment was either acute or chronic. The acute dose (5 mg/kg and 15 mg/kg body weight) was in the form of an injection given intraperitoneally, 30 min before irradiation. The chronic administration was in the form of caffeine solution (4.208 x 10(-3) M and 7.72 x 10(-4) M) contained in the drinking water that mice had had ad libitum access to instead of plain drinking water for 5 weeks prior to radiation exposure. The acute pre-treatment with caffeine reduced the radiation-induced frequency of chromosomal aberrations discernibly, whereas the chronic pre-treatment afforded a much more significant degree of radioprotection. The caffeine post-treatment (5 mg/kg and 15 mg body weight) was given in the form of an intraperitoneal injection to the mice immediately following whole-body gamma-irradiation. It is noted that both post-treatment concentrations of caffeine also significantly reduced the frequency of chromosomal aberrations induced by gamma-rays. These data are briefly discussed in terms of possible mechanistic considerations.     

Genotoxicity of drinking water from three Korean cities

Organic content of drinking tap water from Seoul, Taejon, and Suwon was extracted with an XAD-2 resin column and organic solvents. Four doses of the extract equivalent to 4, 2, 1, and 0.5 l water were tested for mutagenicity in Salmonella typhimurium strains TA98 and TA100 in the presence and absence of S9 mix. The organic extracts of the water from all three cities were mutagenic in TA 98 without S9 mix and in TA 100 with and without S9 mix. The highest number of revertants per plate was found in the absence of S9 mix. Three doses of the extract (equivalent to 22, 11, and 3.7 l water) were also tested in the bone marrow micronucleus test using BDF1 mice. At the highest dose, a significant increase of the micronucleus frequency was observed. The time required to be on the effect, however, varied with the source of the water. Our results indicate that the drinking tap waters from the three cities were genotoxic clearly in the bacterial test and also in the in vivo assay with mice. As we found no genotoxicity of the source water as seen in a previous study, it is likely that the chlorination process leads to the genotoxicity of the tap water.     

Effect of thiourea on intracranial bone tumour formation in AkR mice.

The effect of administration of thiourea (5 g/kg in diet) alone or simultaneously with thyroxine (1 mg/l in drinking water) on the frequency of hyperplastic benign osteoma of the skull was studied in AkR mice. Animals treated with both thiourea and thyroxine were in hyperthyroidism: the thyroxine dose received was higher that that required to prevent thiourea-induced thyroid gland hypertrophy. A significant increase of the intracranial bone tumour (IBT) frequency was observed both in mice treated with thiourea alone and those which received thiourea and thyroxine simultaneously. Increase of IBT frequency was not due to the antithyroid effect of thiourea but seems due to a direct toxic action of thiourea on the pituitary.     

饮酒小鼠动物模型建立及其对雌性激素的影响

目的建立模拟人类饮酒的小鼠动物模型,并以此动物模型进一步研究酒精对小鼠雌激素水平及乳腺癌的影响。方法 SPF级C57BL/6雌性小鼠,随机分对照组和酒精组两组,酒精组20:00到次日8:00给予含有一定浓度酒精的饮用水,其他时间给予常规饮用水,对照组全天给予常规饮用水。观察两组小鼠的饮水量及体重变化;用ANALOX AM1酒精分析仪检测小鼠凌晨2∶00和8∶00血液的酒精浓度(BEC);酶联免疫法(ELASA)检测两组小鼠血清中雌激素水平的差异。结果饮酒组小鼠血液BEC明显增高,类似人类饮酒水平,饮酒组小鼠的饮水量及体重无明显变化;饮酒组小鼠体内雌激素的水平明显高于对照组。结论成功的建立模拟人类饮酒的动物模型,并通过此动物模型初步证实酒精刺激可以增加小鼠体内血清雌激素的水平。     

Analysis of the number of normochromic erythrocytes with micronuclei in the peripheral blood of mice as a method of detecting mutagens

Cytogenic damages both in the bone marrow (5.5-fold increase in the number of cells with chromosomal aberrations) and in the peripheral blood of mice (4.5-fold increase in the frequency of micronuclear polychromatic erythrocytes and 3-fold rise in the number of micronuclear normochromic erythrocytes, as compared to the control) have been observed after a two-week administration of 0.01% cyclophosphamide with drinking water. The micronuclear test on mature erythrocytes from peripheral blood of mice can be an effective method for the identification of mutagenic properties of the factor under study during its long-term action.     

Water economy in a terrestrial toad (Bufo bufo), with special reference to cutaneous drinking and urinary bladder function

Undisturbed toads, acclimated to a simulated terrestrial habitat with access to water, generally visited the water resource for cutaneous drinking before evaporative water losses had resulted in dehydration of the body, and often the bladder still contained ample amounts of urine. The toads did not urinate when they stayed out of water, but exposure to water in the terrestrially-acclimated state facilitated urination, even when the bladder contained only insignificant amounts of urine. Daily emptying of the bladder often resulted in substantial water deficits prior to drinking, but the severity and frequency of the deficits declined with time, concurrently with an increase in the frequency of cutaneous drinking. Volumes of urine stored in the bladder when the toads suspended cutaneous drinking varied from negligible to large, corresponding to up to 20% of the body mass. Daily emptying of the bladder tended to increase the volume of urine stored at the end of drinking episodes. It is concluded that toads and other terrestrial amphibians primarily maintain normal water balance by anticipatory cutaneous drinking; emergency drinking in response to dehydration plays a secondary role.     

Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride.

We have examined the possible effect of fluoride intake on chromosome damage. There was no evidence of increased frequency of chromosomal aberration in bone marrow or testis cells of mice with either 50 ppm fluoride intake over several generations or 100 ppm intake for 6 weeks compared to animals drinking distilled water. Fluoride was not found to be mutagenic in a widely used bacterial mutagenesis assay over a range of 0.1 to as high as 2000 microgram fluoride per plate.     

Effects of sulfadiazine and amprolium on Neospora caninum (Protozoa: Apicomplexa) infections in mice

An immunosuppressed mouse model was used to determine the effects of amprolium and sulfadiazine on experimental Neospora caninum infections. Both drugs were given in the drinking water. Neither drug was effective in treating infections when given 7 days after inoculation of tachyzoites, when clinical signs of disease had developed. Amprolium did not prevent deaths or development of clinical signs when given in the drinking water at 1 mg/ml or 5 mg/ml 3 days after inoculation of tachyzoites. Sulfadiazine in drinking water was not effective when given at 0.5 mg/ml but was effective in preventing deaths and clinical disease when given at 1 mg/ml 3 days after inoculation with tachyzoites. Most mice (6 of 10) treated for 3 days with 1 mg/ml sulfadiazine in drinking water developed encephalitis after drug treatment was stopped. Treatment for 14 days with 1 mg/ml sulfadiazine in drinking water was needed to protect 90% of inoculated mice.     

Lack of cytogenetic effects in mice or mutations in Salmonella receiving sodium fluoride

We have examined the possible effect of fluoride intake on chromosome damage. There was no evidence of increased frequency of chromosomal aberration in bone marrow or testis cells of mice with either 50 ppm fluoride intake over several generations or 100 ppm intake for 6 weeks compared to animals drinking distilled water. Fluoride was not found to be mutagenic in a widely used bacterial mutagenesis assay over a range of 0.1 to as high as 2000 μg fluoride per plate.     

Sister chromatid exchanges in bone marrow cells of mice maintained on tritiated water

The ability of tritium to induce sister chromatid exchanges (SCEs) has been investigated in male mice of the Hale-Stoner-Brookhaven strain maintained on drinking water containing 3.0 microCi/ml tritiated water (HTO). At selected intervals after 28-261 days of consuming HTO, the frequency of SCEs and the kinetics of cellular proliferation were measured in bone marrow cells of animals maintained on HTO, and in age-matched control groups, by 5-bromo-2'-deoxyuridine labelling methods. A statistically significant (1 percent level) elevation of SCEs was observed after 81, 163, 192, 247 and 261 days of HTO ingestion. The frequency of induced SCEs increased linearly with the ingestion time. These results are of particular interest since ionizing radiation is generally not considered to be an efficient inducer of SCEs.     

Depression‐like symptoms of withdrawal in a genetic mouse model of binge methamphetamine intake

Binge methamphetamine (MA) users have higher MA consumption, relapse rates and depression‐like symptoms during early periods of withdrawal, compared with non‐binge users. The impact of varying durations of MA abstinence on depression‐like symptoms and on subsequent MA intake was examined in mice genetically prone to binge‐level MA consumption. Binge‐level MA intake was induced using a multiple‐bottle choice procedure in which mice were offered one water drinking tube and three tubes containing increasing concentrations of MA in water, or four water tubes (control group). In two studies, depression‐like symptoms were measured using a tail‐suspension test and a subsequent forced‐swim test, after forced abstinence of 6 and 30 hours from a 28‐day course of chronic MA intake. An additional study measured the same depression‐like symptoms, as well as MA intake, after prolonged abstinence of 1 and 2 weeks. MA high drinking mice and one of their progenitor strains DBA/2J escalated their MA intake with increasing MA concentration; however, MA high drinking mice consumed almost twice as much MA as DBA/2J mice. Depression‐like symptoms were significantly higher early after MA access was withdrawn, compared to levels in drug‐naïve controls, with more robust effects of MA withdrawal observed in MA high drinking than DBA/2J mice. When depression‐like symptoms were examined after 1 or 2 weeks of forced abstinence in MA high drinking mice, depression‐like symptoms dissipated, and subsequent MA intake was high. The MA high drinking genetic mouse model has strong face validity for human binge MA use and behavioral sequelae associated with abstinence.     

Suppression of atopic dermatitis and tumor metastasis in mice by small amounts of radon

We examined the effect of radon in two experimental disease models in mice by administering radon dissolved in water at 68-203 Bq/liter. Administration of radon in drinking water to NC/Nga mice significantly delayed the progression of atopic dermatitis-like skin lesions induced by picrylchloride when administered prior to the induction of disease signs. The number of pulmonary metastatic foci in C57BL/6 mice inoculated with B16 melanoma cells was also reduced significantly by administration of radon in drinking water when the number of tumor cells was small and the radon treatment was started prior to tumor inoculation. The ratio of Ifng to Il4 produced by splenocytes from BALB/c mice immunized with DNP-Ascaris was significantly increased by administration of radon in drinking water. From these results, a modulation of immunity by radon was suggested.     

The Buzz of Drinking on the Wing in Echolocating Bats

Bats broadcast rapid sequences of echolocation calls, named ‘drinking buzzes’, when they approach water to drink on the wing. So far this phenomenon has received little attention. We recorded echolocation sequences of drinking bats for 12 species, for 11 of which we also recorded feeding buzzes. Based on the different sensorial tasks faced by feeding and drinking bats, we hypothesize that the drinking buzz structure will differ from that of feeding buzzes since unlike the latter drinking buzzes are not designed to detect and track mobile prey. We demonstrated that drinking buzzes are structurally different from feeding buzzes. We show that the buzz‐II phase common in feeding buzzes is absent in drinking buzzes; that is, call frequency is not lowered to broaden sonar beam since the task of drinking does not imply tracking fast‐moving targets. This finding indirectly confirms the role of buzz II in feeding buzzes. Pulse rate in drinking buzzes is also lower than in feeding buzzes, as predicted since the high pulse rate typical of feeding buzzes is important to update rapidly the relative location of moving targets. The most likely function of drinking buzzes is to guide a safe drinking manoeuvre, similar to ‘landing buzzes’ broadcast when bats land on the ground.     

四环素调控SV40Tag转基因小鼠模型的建立

目的构建四环素调控的SV40T转基因小鼠模型。方法同时显微注射外源基因p205-rtTA-C3和pTRE-Tag至FVB小鼠原核,注射受精卵移植到同期发情的假孕受体出生个体,经PCR和Southern检测获得阳性转基因小鼠。结果经PCR结合Southern检测得到rtTA和Tag双阳性转基因小鼠一只,rtTA单阳性两只和Tag单阳性一只。结论通过饮水给与四环素的双阳性小鼠可在卵巢中检测到Tag mRNA的表达。     

Evaluation of antitumor effect of oxygen nanobubble water on breast cancer-bearing BALB/c mice

Hypoxia is a condition of low oxygen level which poses a common feature of most cancers. In the current study, we investigated effect of water containing oxygen nanobubble (ONB) on tumor growth in breast cancer 4T1-bearing mice during 14-day treatment period. Tumor-bearing mice were randomly divided into three groups (six mice per group), including the ONB group drinking water containing ONB, the air nanobubble (ANB) group drinking water containing ANB, and control group drinking normal water. Tumor weight and size were measured in 2-day interval during 14-day treatment. mRNA expression of p53, vascular endothelial growth factor (VEGF), hypoxia-inducible factor (HIF), and cyclin D/Cdk2 genes were measured in the treated and control mice. After 8, 12, and 14 days of treatment, tumor size in ONB group was significantly decreased by 40.5%, 32.8%, and 28%, respectively, when compared with the control group. In addition, ANB group showed a significant reduction in tumor burden as well. The messenger RNA (mRNA) level of p53 in tumor cells of ONB and ANB group was found to be 36-fold (P = 0.0001) and 33-fold (P = 0.0001) higher than that in the control group, respectively. There was a ninefold increase in mRNA expression of VEGF gene in tumor cells of ANB mice than that in control mice; however, there was no significant changes in ONB group. Expression of HIF gene was significantly lower in tumor cells of ONB and ANB group than in the control group. It is concluded that drinking ONB water has potential to inhibit tumor growth, however more preclinical and proof-of-concept studies are needed to confirm its safety and therapeutic effect.     

Distinct ethanol drinking microstructures in two replicate lines of mice selected for drinking to intoxication

The High Drinking in the Dark (HDID) mice have been selectively bred for reaching high blood ethanol concentrations (BECs) following the limited access Drinking in the Dark (DID) test. We have shown previously that mice from the first HDID replicate line (HDID‐1) drink in larger, but not longer, ethanol drinking bouts than the low‐drinking HS/Npt control mice when consuming modest amounts in the DID test. Here, we assessed drinking microstructure in HDID‐1 mice during binge‐like levels of ethanol intake using a lickometer system. Mice from both HDID replicates (HDID‐1 and ‐2) and HS mice were also given three DID tests (single‐bottle ethanol, two‐bottle choice and single‐bottle saccharin) using a continuously recording BioDAQ system to determine whether there are selection‐dependent changes in drinking microstructure. Larger ethanol bout size in the HDID‐1 mice than the HS mice was found to be due to a larger lick volume in these mice. HDID‐1 and HDID‐2 mice were also seen to have different drinking microstructures that both resulted in high intake and high BECs. The HDID‐1 mice drank in larger ethanol bouts than HS, whereas HDID‐2 mice drank in more frequent bouts. This pattern was also seen in two‐bottle choice DID. The HDID‐2 mice had a high bout frequency for all fluid types tested, whereas the large bout size phenotype of the HDID‐1 mice was specific to alcohol. These findings suggest that selection for drinking to intoxication has resulted in two distinct drinking microstructures, both of which lead to high BECs and high ethanol intake.     

Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses

Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10 mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.     

Oral chromium(VI) does not affect the frequency of micronuclei in hematopoietic cells of adult mice and of transplacentally exposed fetuses

Chromium(VI) compounds are genotoxic in a variety of cellular systems. Their potential carcinogenicity is affected by toxicokinetic patterns restricting bioavailability to certain targets, and by metabolic pathways affecting interaction of chromate-derived reactive species with DNA. Epidemiological data indicate that chromium(VI) can be carcinogenic to the human respiratory tract following inhalation at doses that are only achieved in certain occupational settings. However, concern has been raised that adverse effects may also result from oral intake. In order to further explore this issue, we performed studies in BDF1 and Swiss mice of both genders and various age. Sodium dichromate dihydrate and potassium dichromate were administered either with the drinking water, up to a concentration of 500 mg chromium(VI)/l for up to 210 consecutive days, or in a single intragastric dose of 17.7 mg/kg body weight. Under these conditions, no increase of the micronucleus frequency was observed in either bone marrow or peripheral blood erythrocytes. Conversely, the same compounds induced a clastogenic damage following intraperitoneal injection, which by-passes detoxification mechanisms. In addition, due to the hypothesis that susceptibility may be increased during the period of embryogenesis, we treated pregnant mice, up to a concentration of 10mg chromium(VI)/l drinking water. There was no effect on the numbers of fetuses/dam and on body weight of fetuses. Again, no toxic or genotoxic effect was observed either in bone marrow of pregnant mice or in liver and peripheral blood of their fetuses. Thus, even at doses that largely exceed drinking water standards (up to 10,000 times) or by massive intragastric administration, chromium(VI) is not genotoxic to hematopoietic cells of either adult mice or transplacentally exposed fetuses. These conclusions are consistent with the poor toxicity and lack of carcinogenicity of oral chromium(VI), and are mechanistically explained by the high efficiency of chromium(VI) detoxification processes in the gastrointestinal tract.