Benzene is metabolized and covalently bound in bone marrow in situ

Irons, Richard D.; Dent, John G.; Baker, Terrie S.; Rickert, Douglas E.

doi:10.1016/0009-2797(80)90130-1

Cited by 95 publications

(21 citation statements)

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“…In addition, the bone marrow has been shown to convert benzene to its known metabolites (197,198). Irons et al "clearly establish the capability of bone marrow to metabolize benzene independent of metabolism of the compound by the liver" (198). The authors stress, however, that recovered metabolites represented considerably less than 1% of the benzene administered to male F344/N rats.…”

Section: Metabolism or Metabolitesmentioning

confidence: 91%

“…Since then, a number of studies have been published by Williams and co-workers on benzene and other chemicals (196). In addition, the bone marrow has been shown to convert benzene to its known metabolites (197,198). Irons et al "clearly establish the capability of bone marrow to metabolize benzene independent of metabolism of the compound by the liver" (198).…”

Section: Metabolism or Metabolitesmentioning

confidence: 99%

See 1 more Smart Citation

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

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Toxicology and carcinogenesis studies of benzene (CAS No. 71-43-2; greater than 99.7% pure) were conducted in groups of 60 F344/N rats and 60 B6C3FW mice of each sex for each of three exposure doses and vehicle controls. These composite studies on benzene were designed and conducted because of large production volume and widespread human exposure, because of the epidemiologic association with leukemia, and because previ. ous experiments were considered inadequate or inconclusive for determining carcinogenicity in laboratory animals. Using the results from 17-week studies, doses for the 2-year studies were selected based on clinical observations (tremors in higher dosed mice), on clinical pathologic findings (lymphoid depletion in rats and leukopenia in mice), and on body weight effects. Doses of 0, 50, 100, or 200 mg/kg body weight benzene in corn oil were administered by gavage to male rats, 5 days per week, for 103 weeks. Doses of 0, 25, 50, or 100 mg/kg benzene in corn oil were administered by gavage to female rats and to male and female mice for 103 weeks. Ten animals in each of the 16 groups were killed at 12 months, and necropsies were performed. Hematologic profiles were performed at 3-month intervals.For the 2-year studies, mean body weights of the top dose groups of male rats and of both sexes of mice were lower than those of the controls. Survivals of the top dose group of rats and mice of each sex were reduced; however, at week 92 for rats and week 91 for mice, survival was greater than 60% in all groups; most of the dosed animals that died before week 103 had neoplasia. Compound-related nonneoplastic or neoplastic effects on the hematopoietic system, Zymbal gland, forestomach, and adrenal gland were found both for rats and mice. Further, the oral cavity was affected in rats, and the lung, liver, Harderian gland, preputial gland, ovary, and mammary gland were affected in mice. Under the conditions of these 2-year gavage studies, there was clear evidence of carcinogenicity of benzene in male F344/N rats, female F344/N rats, male B6C3FW mice, and female B6C3FM mice. In male rats, benzene caused increased incidences of Zymbal gland carcinomas, squamous cell papillomas and squamous cell carcinomas of the oral cavity, and squamous cell papillomas and squamous cell carcinomas of the skin. In female rats, benzene caused increased incidences of Zymbal gland carcinomas and squamous cell papillomas and squamous cell carcinomas of the oral cavity. In male mice, benzene caused increased incidences of Zymbal gland squamous cell carcinomas, malignant lymphomas, alveolar/bronchiolar carcinomas and alveolar/bronchiolar adenomas or carcinomas (combined), Harderian gland adenomas, and squamous cell carcinomas of the preputial gland. In female mice, benzene caused increased incidences of malignant lymphomas, ovarian granulosa cell tumors, ovarian benign mixed tumors, carcinomas and careinosarcomas of the mammary gland, alveolar/bronchiolar adenomas, alveolar/bronchiolar carcinomas, and Zymbal gland squamous cell carcin...

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Section: Metabolism or Metabolitesmentioning

confidence: 91%

Section: Metabolism or Metabolitesmentioning

confidence: 99%

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Huff

Haseman

DeMarini

et al. 1989

Environ Health Perspect

113

107

View full text Add to dashboard Cite

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“…Decreasing the hepatic metabolism of benzene by partial hepatectomy also reduced benzene toxicity, suggesting that hepatic metabolism plays an important role in toxicity (5). In addition to hepatic metabolism, it appears that secondary metabolism of benzene metabolites in bone marrow contributes to toxicity (6)(7)(8)(9)(10)(11). Thus, elucidation of the metabolic pathway for benzene biotransformation is essential for a full understanding of the mechanism of toxicity.…”

Section: Benzene Metabolism and Toxicitymentioning

confidence: 99%

An Overview of Benzene Metabolism

Snyder¹,

Hedli²

1996

Environ Health Perspect

105

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Benzene toxicity involves both bone marrow depression and leukemogenesis caused by damage to multiple classes of hematopoietic cells and a variety of hematopoietic cell functions. Study of the relationship between the metabolism and toxicity of benzene indicates that several metabolites of benzene play significant roles in generating benzene toxicity. Benzene is metabolized, primarily in the liver, to a variety of hydroxylated and ring-opened products that are transported to the bone marrow where subsequent secondary metabolism occurs. Two potential mechanisms by which benzene metabolites may damage cellular macromolecules to induce toxicity include the covalent binding of reactive metabolites of benzene and the capacity of benzene metabolites to induce oxidative damage. Although the relative contributions of each of these mechanisms to toxicity remains unestablished, it is clear that different mechanisms contribute to the toxicities associated with different metabolites. As a corollary, it is unlikely that benzene toxicity can be described as the result of the interaction of a single metabolite with a single biological target. Continued investigation of the metabolism of benzene and its metabolites will allow us to determine the specific combination of metabolites as well as the biological target(s) involved in toxicity and will ultimately lead to our understanding of the relationship between the production of benzene metabolites and bone marrow toxicity.

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“…Decreasing the hepatic metabolism of benzene by partial hepatectomy also reduced benzene toxicity, suggesting that hepatic metabolism plays an important role in toxicity. In addition to hepatic metabolism, it appears that filtration of benzene and its metabolites contributes to toxicity [8,9]. So in this study the toxic effects of benzene on liver and kidney tissues also investigated.…”

Section: Introductionmentioning

confidence: 97%

The effects of grape seed extract against toxicity of benzene on liver and kidney tissues of albino mice: biochemical evaluation

et al. 2015

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Objective: The objective of the present study was to investigate the possible effects of grape seed extract (GSE) against benzene-induced toxicity in Swiss albino mice. Methods: The animals were randomly divided into six groups each containing six mice. Group I, treated with distilled water; Group II and III orally treated with 50 mg/kg and 150 mg/kg body weight GSE, respectively. Group IV, orally treated with 250 mg/kg body weight benzene by using feeding cannula; Group V, orally treated with 50 mg/kg body weight GSE + 250 mg/kg body weight benzene; Group VI, orally treated with 150 mg/kg body weight GSE + 250 mg/kg of body weight benzene for 50 consecutive days. At the end of experimental period all mice were sacrificed; blood, liver and kidney tissues were removed after post-mortem examination. Aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), blood urea nitrogen (BUN), creatinine levels were analyzed from serum. Malondialdehyde (MDA) and reduced glutathione (GSH) levels were analyzed from isolated tissues. And also histopathological examinations of liver and kidney tissues were investigated. Results: Serum AST, ALT, ALP, BUN and creatinine levels were slightly increased in Group IV compared with the other tested groups (p<.05). Benzene-induced toxicity caused a significant decrease in GSH levels and a significant rise in MDA levels of liver and kidney tissues. Oral treatment with GSE significantly ameliorated the indices of hepatotoxicity, nephrotoxicity and lipid peroxidation induced by benzene. Both doses of GSE provided significant protection and the strongest effects were observed at the dose level of 150 mg/kg. Conclusion: Consequently, it was found that GSE has a significant positive effect in benzeneinduced toxicity, and its GSE effect is dose dependent. Key Words: Benzene, GSH, MDA grape seed Conflict of Interest: The authors have no conflict of interest. ÖZETAmaç: Bu çalışmanın amacı albino farelerde benzen tarafından oluşturulan toksisitesiye karşı üzüm çekirdeği ekstraktının muhtemel etkisini araştırmaktır. Metod: Her bir grupta 6 fare olmak üzere uygulama grupları oluşturulmuştur. Grup I, oral yolla distile su ile; Grup II, oral yolla 50 mg/kg GSE; Grup III, 150 mg/kg GSE; Grup IV, oral yolla kanula kullanılarak 250 mg/kg benzen; Grup V, 50 mg/kg GSE + 250 mg/kg benzen; Grup VI, 150 mg/kg GSE + 250 mg/kg benzen ile 50 gün süre ile beslenmişlerdir. Deney sürelerinin sonunda otopsi yoluyla farelerin kan, karaciğer ve böbrek dokuları alınmıştır. Aspartat aminotransferaz (AST), Alanin aminotransferaz (ALT), Alkalen fosfataz (ALP), kan üre azotu (BUN), kreatinin düzeyleri kan dokudan, malondialdehit (MDA), redükte glutatyon (GSH) ise karaciğer ve böbrek dokularında incelenmiştir. Ayrıca karaciğer ve böbrek dokularında histopatolojik değişimler de araştırılmıştır. Bulgular: Benzen uygulanan farelerde serum AST, ALT, ALP BUN ve kreatinin seviyelerinde kontrol grubuna kıyasla düşük düzeyde artış belirlenmiştir. Benzen tarafından oluşturulan oksidatif to...

show abstract

Benzene is metabolized and covalently bound in bone marrow in situ

Cited by 95 publications

References 4 publications

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

Multiple-site carcinogenicity of benzene in Fischer 344 rats and B6C3F1 mice.

An Overview of Benzene Metabolism

The effects of grape seed extract against toxicity of benzene on liver and kidney tissues of albino mice: biochemical evaluation

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