PMID- 35963423
OWN - NLM
STAT- MEDLINE
DCOM- 20220831
LR  - 20220901
IS  - 1879-3169 (Electronic)
IS  - 0378-4274 (Linking)
VI  - 368
DP  - 2022 Sep 1
TI  - DNA damage, DNA repair gene expression, and topoisomerase IIalpha activity in CD-1 
      mice following in utero benzene exposure.
PG  - 47-55
LID - S0378-4274(22)00979-1 [pii]
LID - 10.1016/j.toxlet.2022.08.002 [doi]
AB  - Benzene is an environmental toxicant and known human carcinogen. Recent 
      epidemiological studies show a relationship between exposure to benzene in 
      pregnant women and increased incidence of childhood leukemias. Studies in murine 
      models demonstrate a relationship between carcinogenicity and in utero benzene 
      exposure which was sex dependent, thus the cellular mechanisms of benzene 
      toxicity by sex require further studies. A hypothesized mechanism of 
      benzene-induced in utero carcinogenicity is through increased DNA damage and 
      reduced fetal DNA repair capacity. This includes the potential inhibition of 
      topoisomerase IIalpha (topo IIalpha), in part, to generate double stranded DNA (dsDNA) 
      breaks and induction of error-prone DNA repair. Using a mouse model of 
      transplacental benzene carcinogenicity, gestational day (GD) 14 fetal livers were 
      harvested 2, 6, and 24 h following maternal exposure to 200 mg/kg benzene and 
      used to assess DNA damage, DNA repair gene expression and topo IIalpha activity. DNA 
      damage, measured by levels of modified histone H2AX (gammaH2AX), is significantly 
      increased in benzene exposed pups, with sex-dependent significance seen only in 
      female pups. Comet assay results confirmed that benzene exposure in utero induces 
      dsDNA damage in the GD14 fetal liver. Genes involved in DNA repair were assessed, 
      and DNA repair gene expression changes were observed after 24 h in genes related 
      to nucleotide excision repair, homologous recombination, and non-homologous 
      end-joining. There were no significant differences in topo IIalpha activity in GD14 
      fetal livers at any timepoint, or between sexes. Overall, this study shows that 
      200 mg/kg benzene exposure induces dsDNA damage and alters fetal DNA repair gene 
      expression in utero, without perturbing fetal topo IIalpha in CD-1 mice.
CI  - Copyright (c) 2022. Published by Elsevier B.V.
FAU - Holmes, Trent H
AU  - Holmes TH
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada.
FAU - Winn, Louise M
AU  - Winn LM
AD  - Department of Biomedical and Molecular Sciences, Queen's University, Kingston, 
      Ontario K7L 3N6, Canada; School of Environmental Studies, Queen's University, 
      Kingston, Ontario K7L 3N6, Canada. Electronic address: winnl@queensu.ca.
LA  - eng
PT  - Journal Article
DEP - 20220811
PL  - Netherlands
TA  - Toxicol Lett
JT  - Toxicology letters
JID - 7709027
RN  - 0 (Antigens, Neoplasm)
RN  - 0 (DNA-Binding Proteins)
RN  - 9007-49-2 (DNA)
RN  - EC 5.99.1.3 (DNA Topoisomerases, Type II)
RN  - J64922108F (Benzene)
SB  - IM
MH  - Animals
MH  - *Antigens, Neoplasm/genetics
MH  - *Benzene/toxicity
MH  - DNA
MH  - *DNA Damage
MH  - *DNA Repair
MH  - *DNA Topoisomerases, Type II/genetics/metabolism
MH  - DNA-Binding Proteins/genetics
MH  - Female
MH  - Gene Expression
MH  - Maternal Exposure
MH  - Mice
MH  - Pregnancy
OTO - NOTNLM
OT  - Benzene
OT  - DNA Damage
OT  - DNA repair
OT  - Fetal
OT  - Topoisomerase IIalpha
EDAT- 2022/08/14 06:00
MHDA- 2022/09/01 06:00
CRDT- 2022/08/13 19:34
PHST- 2022/03/24 00:00 [received]
PHST- 2022/07/16 00:00 [revised]
PHST- 2022/08/08 00:00 [accepted]
PHST- 2022/08/14 06:00 [pubmed]
PHST- 2022/09/01 06:00 [medline]
PHST- 2022/08/13 19:34 [entrez]
AID - S0378-4274(22)00979-1 [pii]
AID - 10.1016/j.toxlet.2022.08.002 [doi]
PST - ppublish
SO  - Toxicol Lett. 2022 Sep 1;368:47-55. doi: 10.1016/j.toxlet.2022.08.002. Epub 2022 
      Aug 11.