DNA damage in intact cells induced by bacterial metabolites of chloramphenicol

M. Isildar, Joaquin J Jimenez, G. K. Arimura, Adel A Yunis

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentration of 10-4 M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 x 10-5 M from 2 x 10-3 M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.

Original languageEnglish
Pages (from-to)40-46
Number of pages7
JournalAmerican Journal of Hematology
Volume28
Issue number1
StatePublished - Jan 1 1988

Fingerprint

Chloramphenicol
DNA Damage
Single-Stranded DNA Breaks
Bone Marrow
Aplastic Anemia
Bone Marrow Cells
Lymphocytes
Bacteria

ASJC Scopus subject areas

  • Hematology

Cite this

DNA damage in intact cells induced by bacterial metabolites of chloramphenicol. / Isildar, M.; Jimenez, Joaquin J; Arimura, G. K.; Yunis, Adel A.

In: American Journal of Hematology, Vol. 28, No. 1, 01.01.1988, p. 40-46.

Research output: Contribution to journalArticle

Isildar, M. ; Jimenez, Joaquin J ; Arimura, G. K. ; Yunis, Adel A. / DNA damage in intact cells induced by bacterial metabolites of chloramphenicol. In: American Journal of Hematology. 1988 ; Vol. 28, No. 1. pp. 40-46.
@article{93258cd752174199990a872a6058b406,
title = "DNA damage in intact cells induced by bacterial metabolites of chloramphenicol",
abstract = "Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentration of 10-4 M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 x 10-5 M from 2 x 10-3 M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.",
author = "M. Isildar and Jimenez, {Joaquin J} and Arimura, {G. K.} and Yunis, {Adel A}",
year = "1988",
month = "1",
day = "1",
language = "English",
volume = "28",
pages = "40--46",
journal = "American Journal of Hematology",
issn = "0361-8609",
publisher = "Wiley-Liss Inc.",
number = "1",

}

TY - JOUR

T1 - DNA damage in intact cells induced by bacterial metabolites of chloramphenicol

AU - Isildar, M.

AU - Jimenez, Joaquin J

AU - Arimura, G. K.

AU - Yunis, Adel A

PY - 1988/1/1

Y1 - 1988/1/1

N2 - Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentration of 10-4 M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 x 10-5 M from 2 x 10-3 M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.

AB - Four chloramphenicol (CAP) metabolites known to be produced by intestinal bacteria were examined with respect to their capacity to induce DNA damage in intact cells. The induction of DNA single-strand breaks in Raji cells, activated human lymphocytes, and human marrow cells was assayed by the alkaline elution technique. One of the four compounds tested, dehydro-CAP, was capable of inducing DNA single-strand breaks in all three cell systems at concentration of 10-4 M. This effect is comparable to that observed previously with nitroso-CAP, the nitroreduction intermediate of CAP. The nitroreduction of dehydro-CAP by human bone marrow cell homogenate was detected by the production of the corresponding amino derivative amounting to 5.6 x 10-5 M from 2 x 10-3 M substrate under aerobic conditions. In sharp contrast, nitroreduction of CAP by bone marrow could not be demonstrated. The genotoxicity of dehydro-CAP, its relative stability compared to the nitroso-CAP, and its nitroreducibility by bone marrow suggest that this bacterial metabolite of CAP may play a key role as a mediator of aplastic anemia in the predisposed host.

UR - http://www.scopus.com/inward/record.url?scp=0023881595&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0023881595&partnerID=8YFLogxK

M3 - Article

VL - 28

SP - 40

EP - 46

JO - American Journal of Hematology

JF - American Journal of Hematology

SN - 0361-8609

IS - 1

ER -