Ingestion of ethanol increases the hematotoxicity of inhaled benzene in C57BL mice

Snyder, Carroll A.; Baarson, Keith A.; Goldstein, Bernard D.; Albert, Roy E.

doi:10.1007/bf01611004

Cited by 19 publications

(4 citation statements)

References 7 publications

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“…In agreement with the concept of Sammet et al (44) that hepatic metabolism plays a very important role in producing benzene-induced hemopoietic disorder, ethanol con sumption potentiated the toxicity of benzene (37,58). In contrast, phenobarbital produced a protective effect on toxicity (21,37).…”

Section: Phenobarbital As a Clue To The Underlying Mechanism Of The Dsupporting

confidence: 72%

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Sato¹,

Nakajima²

1987

Scand J Work Environ Health

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SATO A, NAKAJIMA T. Pharmacokinetics of organic solvent vapors in relation to their toxicit y. Scand J Work Environ Health 13 (1987) 81-93 . The volatility and Iipophilicity by which organi c solvents are distinct from other chemicals constitut e a characteristic pharmacokinetic feature . They enter a living body by inhalation, preferentially distribute in the adipose tissue, and are eliminated by both expirat ion and metabolic degradation. Th is review article is centered on experiment al studies conducted by the authors and their co-workers, and it deals with (i) pharmacokinetic principl es, (ii) partition coefficients in relation to toxicity, (iii) significance of metabolism in the developmen t of organic solvent toxicity, and (iv) environmental factors that alt er the metabolism and toxicity of solvents.

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Section: Phenobarbital As a Clue To The Underlying Mechanism Of The Dsupporting

confidence: 72%

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Sato¹,

Nakajima²

1987

Scand J Work Environ Health

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“…Neither were changes evident after the 11-wk exposure (not illustrated). Only a mild effect on cell recovery was anticipated because our highest concentration of benzene was at least 70 times lower than the benzene concentrations of 300 ppm found by other investigators to suppress cell recovery (Snyder et al, 1981;Baarson et al, 1982;Nakajima et al, 1985;Seidel et al, 1990;Baarson & Snyder, 1991).…”

Section: Recovery Of Spleen Lymphocytes and Nucleated Bone Marrow Cellsmentioning

confidence: 78%

“…Animal studies have demonstrated that ethanol can potentiate the immunosuppressive effects of benzene (Snyder et al, 1981;Baarson et al, 1982;Nakajima et al, 1985;Seidel et al, 1990;Baarson & Snyder, 182 D. H. DAIKER ET AL. 1991).…”

mentioning

confidence: 96%

Effect of Cyp2e1 Induction by Ethanol on the Immunotoxicity and Genotoxicity of Extended Low-Level Benzene Exposure

Bk²,

Ha³

et al. 2000

Journal of Toxicology and Environmental Health, Part A

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Potential additive effects of ethanol consumption, a common life-style factor, and low-level benzene exposure, a ubiquitous environmental pollutant, were investigated. Ethanol is a potent inducer of the cytochrome P-450 2E1 (CYP2E1) enzyme, which bioactivates benzene to metabolites with known genotoxicity and immunotoxicity. A liquid diet containing 4.1% ethanol was used to induce hepatic CYP2E1 activity by 4-fold in female CD-1 mice. Groups of ethanol-treated or pair-fed control mice were exposed to benzene or filtered air in inhalation chambers for 7 h/d, 5 d/wk for 6 or 11 wk. The initial experiment focused on immunotoxicity endpoints based on literature reports that ethanol enhances high-dose benzene effects on spleen, thymus, and bone marrow cellularity and on peripheral red blood cell (RBC) and white blood cell (WBC) counts. No statistically significant alterations were found in spleen lymphocyte cellularity, subtype profile, or function (mitogen-induced proliferation, cytokine production, or natural killer cell lytic activity) after 6 wk of ethanol diet, 0.44 ppm benzene exposure, or both. This observed absence of immunomodulation by ethanol alone, a potential confounding factor, further validates our previously established murine model of sustained CYP2E1 induction by dietary ethanol. Subsequent experiments involved a 10-fold higher benzene level for a longer time of 11 wk and focused on genotoxic endpoints in known target tissues. Bone marrow and spleen cells were evaluated for DNA-protein cross-links, a sensitive transient index of genetic damage, and spleen lymphocytes were monitored for hprt-mutant frequency, a biomarker of cumulative genetic insult. No treatment-associated changes in either genotoxic endpoint were detected in animals exposed to 4.4 ppm benzene for 6 or 11 wk with or without coexposure to ethanol. Thus, our observations suggest an absence of genetic toxicity in CD-1 mice exposed to environmentally relevant levels of benzene with or without CYP2E1 induction.

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“…In previous studies, we demonstrated that cells of the erythroid lineage were particularly susceptible to the combined effects of inhaled benzene and ingested ethanol (Snyder et al 1981; Baarson et al 1982). Particularly striking was the transient appearance of nucleated red cells (normoblasts) in the circulating blood of animals undergoing the combined exposures.…”

Section: Introductionmentioning

confidence: 95%

Evidence for the disruption of the bone marrow microenvironment by combined exposures to inhaled benzene and ingested ethanol

Baarson

Snyder

1991

Arch Toxicol

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Studies have been performed to investigate the effects of combined in vivo exposures to inhaled benzene and ingested ethanol on the earliest known murine erythropoietic precursor cells, the Burst Forming Unit--Erythroid (BFU-E) and the Colony Forming Unit--Erythroid (CFU-E). Previously we had determined that murine erythropoietic cell populations were particularly susceptible to combined benzene + ethanol treatments. The most striking example of erythropoietic disruption was the transient appearance of large numbers of nucleated red cells (normoblasts) in the circulating blood. In the present studies, male C57Bl/6 mice were exposed to 300 ppm benzene via inhalation for 6 h/d x 5 d/wk x 9 wks. Groups of mice were also exposed to 5% ethanol in the drinking water 4 d/wk x 9 wks. Appropriate controls were also maintained. The hematological assays were performed after 1, 4, and 9 weeks of exposure. After 4 weeks of exposure large numbers of normoblasts appeared in the circulating blood of mice exposed to benzene + ethanol. However, there were no corresponding increases in the numbers of the earliest erythroid progenitor cells in the bone marrow. There were, however, marked increases in the numbers of these cells in the spleen. Previous work in this laboratory had confirmed that the marrow was the source of circulating normoblasts among animals exposed to benzene + ethanol. We conclude, therefore, that circulating normoblasts appear in the peripheral blood because of changes in the bone marrow microenvironment rather than as a consequence of increased erythropoietic proliferation in the marrow.

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Ingestion of ethanol increases the hematotoxicity of inhaled benzene in C57BL mice

Cited by 19 publications

References 7 publications

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Pharmacokinetics of organic solvent vapors in relation to their toxicity.

Effect of Cyp2e1 Induction by Ethanol on the Immunotoxicity and Genotoxicity of Extended Low-Level Benzene Exposure

Evidence for the disruption of the bone marrow microenvironment by combined exposures to inhaled benzene and ingested ethanol

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