Chemistry Reference
In-Depth Information
Exposure towards arsenicals
Metabolism
in vivo
Inorganic and organic trivalent and pentavalent arsenicals
Oxidative stress, protein binding, altered DNA methylation
•
Alteration of gene expression
•
DNA damage, protein oxidation, lipid peroxidation
•
Modulation of signal transduction pathways
•
Inhibition of DNA repair
Persistence of DNA lesions, mutations, chromosomal damage, upregulation of stress proteins and
protooncogenes, downregulation of tumour suppressor genes, modulation of cell cycle
Accumulation of mutations, enhanced cell poliferation
Carcinogenicity, cocarcinogenicity
Figure 18.2
Major mechanisms in arsenic induced carcinogenicity
Abbreviations
2 - AAAF
2 - acetoxyacetylaminofl uorene
AP - 1
activator protein - 1
APE1
AP - endonuclease 1
AS3MT
arsenic (+3 oxidation state) methyltransferase
ATG
arsenite triglutathione
B[
a
]P
benzo
[
a
]
pyrene
BER
base excision repair
BPDE
benzo
[
a
]
pyrene diolepoxide
CA
chromosomal aberrations
DMA
V
dimethylarsinic acid
DMA
III
dimethylarsinous acid
DMAG
dimethylarsinic glutathione
GSH
glutathione
GST w
glutathione S - transferase w
ERCC1
excision repair cross-complementing rodent repair defi ciency
complementation group 1
