PMID- 16311012
OWN - NLM
STAT- MEDLINE
DCOM- 20060809
LR  - 20131121
IS  - 0887-2333 (Print)
IS  - 0887-2333 (Linking)
VI  - 20
IP  - 5
DP  - 2006 Aug
TI  - Evaluation of cytogenetic and DNA damage induced by the antibacterial drug, 
      trimethoprim.
PG  - 601-7
AB  - Trimethoprim, a widely used antimicrobial drug was tested for its effect on the 
      level of nuclear DNA damage in cultured peripheral blood lymphocytes in terms of 
      chromosome and DNA alterations. The extent of cytogenetic damage, expressed as 
      chromosome breakage and chromosome loss, was evaluated employing the cytokinesis 
      block micronucleus method (CBMN) in cultured peripheral blood lymphocytes coupled 
      with fluorescence in situ hybridization (FISH) using a digoxigenin-labelled 
      alphoid DNA probe specific for the centromere of all human chromosomes. The DNA 
      breakage level was evaluated by the Comet assay. Cultures were set up by using 
      blood samples from two healthy donors. A range of concentrations of the test 
      agent (from 1 to 100 microg/ml) was used for the micronuclei (MN) frequency and 
      cytogenetic origin of MN. For the Comet assay the range of doses used was from 
      0.5 to 150 microg/ml. From the results obtained it appears that this antifolic 
      agent has a significant clastogenic potential, as detected by a dose-dependent 
      increase of the incidence of C-MN and significantly greater than control levels 
      at the highest concentrations tested (25,100 microg/ml). In addition, the results 
      obtained in the Comet assay also show that trimethoprim induces a dose-dependent 
      increase in the level of DNA breakage, this increase attaining statistical 
      significance at the highest concentrations tested (25, 100, 150 microg/ml), which 
      would confirm its genotoxicity.
FAU - Abou-Eisha, A
AU  - Abou-Eisha A
AD  - Department of Cell Biology, National Research Center, Dokki, Cairo, Egypt. 
      aaboueisha@hotmail.com
LA  - eng
PT  - Journal Article
DEP - 20051128
PL  - England
TA  - Toxicol In Vitro
JT  - Toxicology in vitro : an international journal published in association with 
      BIBRA
JID - 8712158
RN  - 0 (Anti-Infective Agents, Urinary)
RN  - AN164J8Y0X (Trimethoprim)
SB  - IM
MH  - Anti-Infective Agents, Urinary/*toxicity
MH  - *Chromosome Aberrations
MH  - Chromosome Breakage
MH  - Comet Assay
MH  - DNA Damage/*drug effects
MH  - Dose-Response Relationship, Drug
MH  - Humans
MH  - In Situ Hybridization
MH  - Lymphocytes/drug effects/ultrastructure
MH  - Micronucleus Tests
MH  - Trimethoprim/*toxicity
EDAT- 2005/11/29 09:00
MHDA- 2006/08/10 09:00
CRDT- 2005/11/29 09:00
PHST- 2005/04/11 00:00 [received]
PHST- 2005/09/14 00:00 [revised]
PHST- 2005/10/15 00:00 [accepted]
PHST- 2005/11/29 09:00 [pubmed]
PHST- 2006/08/10 09:00 [medline]
PHST- 2005/11/29 09:00 [entrez]
AID - S0887-2333(05)00224-9 [pii]
AID - 10.1016/j.tiv.2005.10.008 [doi]
PST - ppublish
SO  - Toxicol In Vitro. 2006 Aug;20(5):601-7. doi: 10.1016/j.tiv.2005.10.008. Epub 2005 
      Nov 28.