The effect of benzene in the micronucleus test

Hite, Mark; Pecharo, Marie; Smith, Inez; Thornton, Susan M.

doi:10.1016/0165-1218(80)90132-9

Cited by 57 publications

(19 citation statements)

References 10 publications

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“…Hite et al [1980] reported significant increases in the number of PCEs with MN in both male and female CD-1 mice given 125 p1 BZ/kg/day by gavage and sacrificed 18 hr after the second dose. Similarly, Meyne and Legator [1980] found that male CD-1 mice exhibited higher frequencies of chromosome aberrations and MN than females after exposure to 500 pl BZ/kg/day by gavage or intraperitoneal injections at 24-hr intervals for 3 consecutive days.…”

Section: Discussionmentioning

confidence: 95%

Induction of cytogenetic damage in rodents after short‐term inhalation of benzene

et al. 1986

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Experiments were designed to investigate both the induction of sister chromatid exchanges (SCEs) in peripheral blood lymphocytes (PBLs) and micronuclei (MN) in bone marrow polychromatic erythrocytes (PCEs) of mice and rats after inhalation of benzene (BZ). Male DBA/2 mice (17-19 weeks old) were exposed to target concentrations of either 0, 10, 100, or 1,000 ppm BZ for 6 hr. Male Sprague-Dawley rats (11-14 weeks old) were exposed to target concentrations of either 0, 0.1, 0.3, 1, 3, 10, or 30 ppm BZ for 6 hr. Blood was obtained by cardiac puncture 18 hr after exposure, and PBLs were cultured in the presence of lipopolysaccharide (mouse B cells, 60 micrograms/ml) or concanavalin A (rat T cells, 30 micrograms/ml) to stimulate blastogenesis for SCE analysis. Femoral bone marrow smears from both species were analyzed for MN in PCEs 18 hr after BZ exposure. Mouse PBLs revealed a significant concentration-related increase in the SCE frequency over controls at 10, 100, or 1,000 ppm BZ. Mouse bone marrow showed a significant concentration-dependent increase in MN over controls after exposure to 10, 100, or 1,000 ppm BZ. Rat PBLs showed a significant increase in the SCE frequency after exposure to 3, 10, or 30 ppm BZ. The statistical significance of the 1 ppm BZ result was borderline and dependent on the statistical test chosen. Rat cells revealed a significant concentration-related increase in MN after inhalation of either 1, 3, 10, or 30 ppm BZ. PBLs from treated mice showed significant concentration-dependent decreases in mitotic indices; however, cell cycle kinetics and leucocyte counts remained unaffected. Rat PBLs showed significant decreases in mitotic activity only after exposure to 3 and 30 ppm BZ, whereas cell cycle kinetics and leucocyte counts were unaffected. These results show that BZ can induce statistically significant cytogenetic effects in PBLs and PCEs of both mice and rats after a 6-hr inhalation of BZ at low concentrations.

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Section: Discussionmentioning

confidence: 95%

Induction of cytogenetic damage in rodents after short‐term inhalation of benzene

et al. 1986

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“…In their work on micronuclei induction in polychromatic erythrocytes . of CD-1 mice Hite et al (1980) reported very large fluctuations in each time group afteroral treatment, but the averagetrendwas flattening of the response above 110 mg/kg, corresponding to approximately 47 ppm accordip.g to EPA computations (Lee et al 1983) (see also legend ofTable 3). Carcinogenic potency of mutagens in rodents seems to correlate semiquantitatively with adduct formation in liver DNA.…”

Section: Short-term Testsmentioning

confidence: 99%

Possible implications from results of animal studies in human risk estimations for benzene: nonlinear dose-response relationship due to saturation of metabolism

Grilli

Lutz

Parodi

1987

J Cancer Res Clin Oncol

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Summary. To date, all risk assessment studies on benzene have been based almost exclusively on epiderniological data. Wehave attempted a more integrated and quantitative evaluation of carcinogenic risk for hurnans, trying to utilize, in addition to the epidemiological data, all data available, specifically data on metabolism, genotoxicity, and carcinogenicity in small rodents. An integrated evaluation of the globality of the available data seems to suggest a progressive saturation of metabolic capacity both for man and rodents between 10 and 100 ppm. The most susceptible target cells seem tobe different in humans (predominant induction of myelogenous leukemia) and small rodents (induction of a wide variety of tumors). Nevertheless, both epidemiological and experimental carcinogenicity data tend to indicate a flattening ofthe response for the highest dosages, again suggesting a general Saturation of mechanisms of metabolic activation, extended to different target tissues. From a quantitative point of view, the data suggest a carcinogenic potency at 10 ppm two to three times higher than that computable by a linear extrapolation from data in the 100 ppm range. These observations are in accord with the recent proposal of the European Economic Community of reducing benzene time-weighted average occupationallevels from 10 to 5 ppm.

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“…An increase in MN frequencies has been observed in bone marrow PCE of mice after acute exposure to benzene p i a z et al., 1979;Hite et al, 1980;Meyne and Legator, 1980;Siou et al, 1981;Gad-El Karim et al, 1984;Tice et al, 19841 and in blood NCE of chronically exposed mice [Choy et al, 1985;Barale et al, 19851. Choy et al [ 19851 reported a dosedependent increase in MN in NCE after mice were chronically exposed 5 times per week for 120 days, 12 months, and 24 months.…”

Section: Introductionmentioning

confidence: 92%

Persistence of micronuclei in peripheral blood normochromatic erythrocytes of subchronically benzene‐treated male mice

Rithidech¹,

Au²,

Ramanujam³

et al. 1988

Environ. mutagen

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The kinetics of micronucleus (MN) induction and decline in blood normochromatic erythrocytes (NCE) of mice subchronically exposed to benzene was investigated during and after exposure. Swiss (ICR) male mice (lO/group) were given 0.0,36.6,73.2, and 146.4 mglkg body weight benzene by gavage daily for 14 days, except for days 5 and 10. The frequency of MN increased significantly (P < .001) during benzene treatment as a function of both concentration and time. Eleven days after exposure the levels of MN were higher than those observed at the end of exposure. After an initial rapid decline in the frequency of MN from 11 to 18 days postexposure, the decline became linear with time through 60 days postexposure. Using linear regression analysis, the MN level in each treatment group was predicted to reach control levels by approximately 85 days post-treatment. Dose-dependent suppression and recovery of erythropoiesis, estimated by polychromatic erythrocyte frequency, were observed in the 1st and 2nd weeks of exposure, respectively. Red blood cell (RBC) production was markedly increased in the first 3 weeks after benzene treatment. At later times the rate of production of the RBC returned to normal and may account for the linear decline observed in MN frequency. This research indicates that the frequency of MN is dose and duration dependent, while the decline in MN frequency after the end of benzene exposure can be related to changes in the kinetics of erythropoiesis.

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The effect of benzene in the micronucleus test

Cited by 57 publications

References 10 publications

Induction of cytogenetic damage in rodents after short‐term inhalation of benzene

Induction of cytogenetic damage in rodents after short‐term inhalation of benzene

Possible implications from results of animal studies in human risk estimations for benzene: nonlinear dose-response relationship due to saturation of metabolism

Persistence of micronuclei in peripheral blood normochromatic erythrocytes of subchronically benzene‐treated male mice

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