The bone marrow as a metabolic organ

Levere, Richard D.; Ibraham, N G

doi:10.1016/0002-9343(82)90399-0

Cited by 12 publications

(5 citation statements)

References 7 publications

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“…The cells were cultured using methods and materials similar to those described by Ryan et al,! 7 and the cultures were observed microscopically at 4 days and at 14 days, when they reached confluency.…”

Section: P-450 In Intimal Cellsiabraham Et Almentioning

confidence: 99%

“…4 However, various extrahepatic tissues, including lung, kidney, intestine, bone marrow, and adrenal glands, contain substantial amounts of cytochrome P-450 mixed function oxidase (MFO) activity. 5 " 7 Ullrich and Graf 8 have shown the presence of cytochrome P-450 in hog aorta microsomes. In their study, they were unable to demonstrate monooxygenase activity using typical substrates for microsomal cytochrome P-450 reactions.…”

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confidence: 99%

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Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Abraham¹,

Pinto²,

Mullane³

et al. 1985

Hypertension

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SUMMARY Cytochrome P-450-dependent mixed function oxidase activity is present in vascular tissue; however, as far as we could determine, the distribution of monooxygenase activity across the blood vessel wall has not previously been assessed. The aryl-hydrocarbon hydroxylase activity was examined by metabolism of benzo[a]pyrene in microsomes prepared from intimal and smooth muscle cell scrapings of the hog thoracic aorta. Microsomes of intimal cells comprising 95 % endothelial cells showed an approximately 2.5-fold increase in aryl-hydrocarbon hydroxylase activity compared with that in microsomes prepared from medial smooth muscle cells. Michaelis-Mentin kinetics for the intimal enzyme yielded an apparent K m value of 11.11 /xM and an apparent V max of 3-0H benzo[a]pyrene of 40 pmol/mg protein/10 min. Aryl-hydrocarbon hydroxylase activity was dependent on nicotinamide adenine dinucleotide phosphate and was inhibited by 7,8 benzoflavone, SKF 525A, and carbon monoxide. The localization of cytochrome P-450-dependent mixed function oxidase primarily to the intimal surface of the aorta may indicate a role for this enzyme system in vasoregulation and the pathogenesis of atherosclerosis. (Hypertension 7: 899-904, 1985)

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Section: P-450 In Intimal Cellsiabraham Et Almentioning

confidence: 99%

mentioning

confidence: 99%

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Abraham¹,

Pinto²,

Mullane³

et al. 1985

Hypertension

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“…Information on the capacity of the bone marrow to metabolize xenobiotics is limited. The presence and induction of aminopyrine‐ N ‐demethylase, a CYP‐dependent enzyme, has been demonstrated in rat bone marrow microsomes ( Levere & Ibrahim, 1982). In addition, immunoblot analysis of rabbit bone marrow microsomal preparations have revealed the presence of CYP2E1 and CYP1A1; the former was induced 12·9‐fold by acetone treatment and the latter 11‐fold by Aroclor 1254 pretreatment ( Schnier et al , 1989 ).…”

mentioning

confidence: 99%

Demonstration of mRNA for five species of cytochrome P450 in human bone marrow, bone marrow‐derived macrophages and human haemopoietic cell lines

Hodges¹,

Molloy²,

Wickramasinghe³

2000

Br J Haematol

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Summary. The expression of mRNA for ®ve cytochrome P450s (CYP1A1, 2A6/7, 2D6, 2E1 and 3A4) was studied in human bone marrow, bone-marrow-derived macrophages and blood monocyte-derived macrophages. Reverse transcriptase polymerase chain reaction (RT-PCR) detected expression of all ®ve CYPs in each of these cell populations. All ®ve CYPs were also expressed in the haemopoietic cell lines HL-60 and HEL and in Epstein±Barr virus (EBV)-transformed B-lymphoblastoid cell lines. The data suggest that bone marrow macrophages and probably other bone marrow cell types are capable of metabolizing xenobiotics. This metabolic potential may play a role in the bone marrow damage induced by some drugs and chemicals.

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“…Such active metabolites would have short half-lives, sugesting activation probably occurs at the target cell site. This is known to occur, for example, with chloramphenicol which undergoes bioreductive activation in the bone marrow resulting in selective toxicity to blood forming tissues (Levene and Ibrahim 1982). Similar severe bone marrow suppression and gastrointestinal damage als0 occur following exposure to mitomycin c, which is activated by a reductive mechanism (Lown 1979).…”

Section: Lesions To Bone Marrow Olfactory Epithelium and Gut Caused mentioning

confidence: 99%

Acute lesions in rats caused by 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) or nitromin: a comparison with rates of reduction in microsomal systems from target organs

et al. 1992

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Pathological lesions to male Fischer rats were investigated 24 h after the administration of 3-amino-1,2,4-benzotriazine-1,4- dioxide (SR 4233) or nitromin, two compounds which need to undergo bioreductive activation in order to exert their toxic effects. Although SR 4233 reduction leads to a putative free radical species while with nitromin a bifunctional alkylating agent is formed, in both instances, the bone marrow was a major target organ. However, the response of other organs to these compounds differed. SR 4233 caused lesions to the olfactory epithelium, liver, kidney and thymus. Nitromin caused focal haemorrhages on the intestine, which were reduced in germ-free rats. Rates of reduction of SR 4233 or nitromin were determined under anaerobic conditions using microsomal preparations from target tissues. With SR 4233 as a substrate, reductase activities were highest in the olfactory epithelium, 6 fold higher than in the liver. SR 4233 reductase activities generally correlated with those of NADPH:cytochrome c reductase or the concentration of cytochrome P-450 reductase protein in the affected organs while with nitromin, there appeared to be no such relationship. The present results support the concept that the expression of pathological damage in vivo is a multifactorial process and does not directly correlate with initial rates of reduction of either drug determined in vitro.

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The bone marrow as a metabolic organ

Cited by 12 publications

References 7 publications

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Presence of cytochrome P-450-dependent monooxygenase in intimal cells of the hog aorta.

Demonstration of mRNA for five species of cytochrome P450 in human bone marrow, bone marrow‐derived macrophages and human haemopoietic cell lines

Acute lesions in rats caused by 3-amino-1,2,4-benzotriazine-1,4-dioxide (SR 4233) or nitromin: a comparison with rates of reduction in microsomal systems from target organs

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