The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice

Luke, Carol A.; Tice, Raymond R.; Drew, Robert T.

doi:10.1016/0165-1161(88)90018-0

Cited by 36 publications

(29 citation statements)

References 18 publications

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“…19,20) Our study revealed a capacity of the tested antidepressant to increase the number of micronuclei in recently formed erythrocytes as shown in the acute assay, where bone marrow damage should have occurred 1-2 d prior to sampling. 21) In this assay, a significant elevation of MNPE was observed with the three tested doses. Moreover, the evaluation of the total genotoxic efficiency indicated high micronuclei induction since the first tested dose.…”

Section: Discussionmentioning

confidence: 90%

“…21,22) This is a potentially relevant observation because of the possible implications in long term treatments of depression, where such repetitive and cumulative damage could have some significance for the future health status. Our micronuclei results showed no lineal dose response among the induction exerted by the three doses of duloxetine, a result that seems to be in line with the saturation effect observed in the acute assay, and whose subjacent explanation can be related with an overwhelming of the enzymatic rate involved in processes such as DNA repair, biotransformation, or detoxification of duloxetine.…”

Section: Discussionmentioning

confidence: 99%

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Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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Duloxetine is a widely used antidepressant worldwide. In the present report, we evaluated its capacity to induce micronucleated polychromatic erythrocytes (MNPEs) and micronucleated normochromatic erythrocytes (MNNEs) in mice. Two assays were performed, one with a single chemical administration and the other with daily chemical administration. In the first, we administered the antidepressant once to groups of 5 mice by the intragastric (i.g.) route (2, 20, and 200 mg/kg) and performed the analysis at 24, 48, and 72 h postadministration. A control group administered i.g. distilled water was included in the assay, as well as another treated with the micronuclei-inducing chemical daunorubicin (2.5 mg/kg, injected intraperitoneally (i.p.)). In this assay, we found significant damage induced by duloxetine starting from the first time evaluated, showing the highest MNPE increase at the end of the assay. We observed a saturation effect as well, suggested by a decreasing relative efficiency with respect to each tested dose. In a second assay, we administered the antidepressant i.g. every day for 5 weeks (2, 6, and 12 mg/kg), and micronuclei analysis was performed at the end of each week. In this study, we also found a significant increase in both MNPEs and MNNEs which was clear by the second week of administration. Our results suggest that short-term as well as cumulative damage is produced by duloxetine. Thus, confirmation of the observed genotoxic potential in other models seems advisable, as well as caution when prescribing this antidepressant.

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Section: Discussionmentioning

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Madrigal-Bujaidar

Álvarez-González

Morales-González

2015

Biological & Pharmaceutical Bulletin

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“…For example, Benson et al (1987) and Dunnick et al (1989) used B6C3F 1 mice to study the toxicity of inhaled nickel subsulfide, nickel oxide, and nickel hexahydrate, and Korsak et al (1998) used BALB/c mice to study the acute toxicity of inhaled 1-methylnapththalene and 2-methylnaphthalene. It has also been observed that B6C3F 1 , C57B1/6, and DBA/2 mice demonstrate different induction levels of genotoxicity and hematotoxicity to chronic inhalation of benzene (Luke et al, 1988). More recently, Fernandez et al (1999) found differences in responses of two mouse strains (BALB/c and C57BL/6) to two common inhaled spasmogens: carbachol and serotonin.…”

Section: Tion; Lung Castsmentioning

confidence: 95%

Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties

Oldham

Phalen

2002

Anat. Rec.

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Strain-and variety-related differences in responses of mice have been reported for a variety of inhaled particulate and gaseous materials. It is important to understand the potential contributions to such responses of differences in delivered doses to the respiratory tract as well as differences in biochemical processes. Deposition doses of inhaled particles are influenced by several factors, including airway anatomy, ventilation, and particle characteristics. Tracheobronchial airway morphometry for airway generations 1-6 of the BALB/c mouse was generated using replica lung casts prepared in situ. Measurements were performed on two groups: control and ovalbumin-sensitized male BALB/c mice. These measurements were compared with previously published airway morphometry of male B6C3F 1 mice. Sensitization did not significantly change measured airway dimensions in the BALB/c mouse. However, the two mouse varieties had significant differences in airway anatomy. The differences found in airway anatomy between mouse varieties correlated with differences in body length and chest circumference. Particle deposition predictions for both varieties of mice were performed for unit density spherical particles from 0.1 to 10 m in diameter at two ventilation rates using a published aerosol dosimetry computer code. Particle deposition in the proximal tracheobronchial tree ranged up to 3 times greater for the BALB/c mouse for a 2 m particle diameter and high ventilation rate. These differences in predicted particle deposition suggest that observed strain and variety differences in response to inhaled particulate matter may be in part due to differences in delivered doses to the respiratory tract. Anat Rec 268: 59 -65, 2002.

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“…The liver is the main hematopoietic organ from the 11th day of gestation until the first days after birth (Keller et al 1999, Udroiu et al 2006, whereas in adult life this role is played by the bone marrow. While micronucleated erythrocytes from the hemopoietic organ reflect genotoxic damage which occurred in the last 48 h, those from peripheral circulation reflect events that occurred during the last 35 days (Schlegel & MacGregor 1982, Luke et al 1988. Finally, it must be underlined that newborn mice, because of their accelerated erythropoiesis, are extremely sensitive to the induction of micronuclei (Bishop et al 2004).…”

Section: Introductionmentioning

confidence: 99%

Clastogenicity and aneuploidy in newborn and adult mice exposed to 50 Hz magnetic fields

Udroiu

Cristaldi

Ieradi

et al. 2006

International Journal of Radiation Biology

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Purpose: To detect possible clastogenic and aneugenic properties of a 50 Hz, 650 mT magnetic field. Materials and methods: The micronucleus test with CREST (Calcinosis, Raynaud's phenomenon, Esophageal dismotility, Sclerodactility, Telangectasia) antibody staining was performed on liver and peripheral blood sampled from newborn mice exposed to an ELF (Extremely Low Frequency) magnetic field during the whole intra-uterine life (21 days), and on bone marrow and peripheral blood sampled from adult mice exposed to the same magnetic field for the same period. Results: Data obtained in newborn mice show a significant increase in micronuclei frequencies. In absolute terms, most of the induced micronuclei were CREST-negative (i.e., formed by a chromosome fragment). However, in relative terms, ELF exposure caused a two-fold increase in CREST-negative micronuclei and a four-fold increase in CREST-positive micronuclei (i.e., formed by a whole chromosome). No significant effect was recorded on exposed adults. Conclusions: These findings suggest the need for investigation of aneugenic properties of ELF magnetic fields in order to establish a possible relationship to carcinogenesis.

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The effect of exposure regimen and duration on benzene-induced bone marrow damage in mice

Cited by 36 publications

References 18 publications

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Evaluation of Duloxetine as Micronuclei Inducer in an Acute and a Subchronic Assay in Mouse

Dosimetry implications of upper tracheobronchial airway anatomy in two mouse varieties

Clastogenicity and aneuploidy in newborn and adult mice exposed to 50 Hz magnetic fields

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