PMID- 16713212
OWN - NLM
STAT- MEDLINE
DCOM- 20060926
LR  - 20131121
IS  - 0940-2993 (Print)
IS  - 0940-2993 (Linking)
VI  - 58
IP  - 1
DP  - 2006 Aug
TI  - Benzene metabolites induce apoptosis in lymphocytes.
PG  - 65-70
AB  - Benzene is an important environmental pollutant with important health 
      implications. Exposure to this aromatic hydrocarbon is associated with 
      hematotoxicity, and bone marrow carcinogenic effects. It has been shown that 
      benzene induces oxidative stress, cell cycle alterations, and programmed cell 
      death in cultured cells. Hepatic metabolism of benzene is thought to be a 
      prerequisite for its bone marrow toxicity. Nevertheless, there are no reports on 
      the cellular effects of reactive intermediates derived from hepatic metabolism of 
      benzene. Thus, the goal of this project was to determine the cellular alterations 
      of benzene metabolites produced by the cultured hepatic cell line HepG2. 
      Supernatants collected from these cells were applied to a culture of freshly 
      isolated lymphocytes. A higher decrease in cell viability was found in cells 
      exposed to these supernatants than to unmetabolized benzene. This viability 
      decrease was due to apoptosis, as determined by Terminal deoxynucleotidyl 
      Transferase Biotin-dUTP Nick End Labeling (TUNEL) assay and internucleosomal 
      fragmentation of DNA. When supernatants were analyzed by HPLC, we found that not 
      all the hydrocarbon was biotransformed, since a 28 microM concentration (37%) 
      remained. The only metabolite found in the culture medium was muconic acid. The 
      present results show that muconic acid derived from benzene metabolism is able to 
      cooperate with the pollutant for the induction of apoptosis in rat lymphocytes.
FAU - Martinez-Velazquez, M
AU  - Martinez-Velazquez M
AD  - Laboratorio de Biologia Molecular, Division de Investigacion Basica, Instituto 
      Nacional de Cancerologia. Av. San Fernando 22 Tlalpan, 14080 Mexico, D.F. Mexico.
FAU - Maldonado, V
AU  - Maldonado V
FAU - Ortega, A
AU  - Ortega A
FAU - Melendez-Zajgla, J
AU  - Melendez-Zajgla J
FAU - Albores, A
AU  - Albores A
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060518
PL  - Germany
TA  - Exp Toxicol Pathol
JT  - Experimental and toxicologic pathology : official journal of the Gesellschaft fur 
      Toxikologische Pathologie
JID - 9208920
RN  - 0 (Benzene Derivatives)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Environmental Pollutants)
RN  - J64922108F (Benzene)
SB  - IM
MH  - Animals
MH  - Apoptosis/*drug effects
MH  - Benzene/*metabolism/toxicity
MH  - Benzene Derivatives/*toxicity
MH  - Carcinoma, Hepatocellular/drug therapy/metabolism
MH  - Cell Line, Tumor
MH  - Cell Nucleus/drug effects/pathology
MH  - Cell Survival/drug effects
MH  - Culture Media, Conditioned/chemistry/metabolism/pharmacology
MH  - Environmental Pollutants/*metabolism/toxicity
MH  - Hepatocytes/drug effects/*metabolism/pathology
MH  - Lymphocytes/*drug effects/pathology
MH  - Male
MH  - Rats
MH  - Rats, Wistar
EDAT- 2006/05/23 09:00
MHDA- 2006/09/27 09:00
CRDT- 2006/05/23 09:00
PHST- 2006/02/01 00:00 [received]
PHST- 2006/03/30 00:00 [accepted]
PHST- 2006/05/23 09:00 [pubmed]
PHST- 2006/09/27 09:00 [medline]
PHST- 2006/05/23 09:00 [entrez]
AID - S0940-2993(06)00045-5 [pii]
AID - 10.1016/j.etp.2006.03.010 [doi]
PST - ppublish
SO  - Exp Toxicol Pathol. 2006 Aug;58(1):65-70. doi: 10.1016/j.etp.2006.03.010. Epub 
      2006 May 18.