TY - JOUR
T1 - Glycidamide and cis-2-butene-1,4-dial (BDA) as potential carcinogens and promoters of liver cancer - An in vitro study
AU - Gouveia-Fernandes, Sofia
AU - Rodrigues, Armanda
AU - Nunes, Carolina
AU - Charneira, Catarina
AU - Nunes, João
AU - Serpa, Jacinta
AU - Antunes, Alexandra M.M.
N1 - Funding Information:
We thank Fundação para a Ciência e a Tecnologia (FCT) , Portugal, for financial support through projects UIDB/QUI/00100/2020 , UIDP/00100/2020 (to CQE), LA/P/0056/2020 (to IMS) and PTDC/QUI-QAN/32242/2017 , as well as contract CEECIND/02001/2017 (to A.M.M.A) and doctoral fellowship SFRH/BD/140157/2018 (to J. N.). NOVA Medical School and IPOLFG are funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência , Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health ( UIDB/04462/2020 and UIDP/04462/2020 ) and the Associated Laboratory LS4FUTURE ( LA/P/0087/2020 ).
Funding Information:
We thank Fundação para a Ciência e a Tecnologia (FCT), Portugal, for financial support through projects UIDB/QUI/00100/2020, UIDP/00100/2020 (to CQE), LA/P/0056/2020 (to IMS) and PTDC/QUI-QAN/32242/2017, as well as contract CEECIND/02001/2017 (to A.M.M.A) and doctoral fellowship SFRH/BD/140157/2018 (to J. N.). NOVA Medical School and IPOLFG are funded by Fundação para a Ciência e Tecnologia/Ministério da Ciência, Tecnologia e Ensino Superior (FCT/MCTES, Portugal) through national funds to iNOVA4Health (UIDB/04462/2020 and UIDP/04462/2020) and the Associated Laboratory LS4FUTURE (LA/P/0087/2020).
Publisher Copyright:
© 2022
PY - 2022/8
Y1 - 2022/8
N2 - Acrylamide and furan are environmental and food contaminants that are metabolized by cytochrome P450 2E1 (CYP2E1), giving rise to glycidamide and cis-2-butene-1,4-dial (BDA) metabolites, respectively. Both glycidamide and BDA are electrophilic species that react with nucleophilic groups, being able to introduce mutations in DNA and perform epigenetic remodeling. However, whereas these carcinogens are primarily metabolized in the liver, the carcinogenic potential of acrylamide and furan in this organ is still controversial, based on findings from experimental animal studies. With the ultimate goal of providing further insights into this issue, we explored in vitro, using a hepatocyte cell line and a hepatocellular carcinoma cell line, the putative effect of these metabolites as carcinogens and cancer promoters. Molecular alterations were investigated in cells that survive glycidamide and BDA toxicity. We observed that those cells express CD133 stemness marker, present a high proliferative capacity and display an adjusted expression profile of genes encoding enzymes involved in oxidative stress control, such as GCL-C, GSTP1, GSTA3 and CAT. These molecular changes seem to be underlined, at least in part, by epigenetic remodeling involving histone deacetylases (HDACs). Although more studies are needed, here we present more insights towards the carcinogenic capacity of glycidamide and BDA and also point out their effect in favoring hepatocellular carcinoma progression.
AB - Acrylamide and furan are environmental and food contaminants that are metabolized by cytochrome P450 2E1 (CYP2E1), giving rise to glycidamide and cis-2-butene-1,4-dial (BDA) metabolites, respectively. Both glycidamide and BDA are electrophilic species that react with nucleophilic groups, being able to introduce mutations in DNA and perform epigenetic remodeling. However, whereas these carcinogens are primarily metabolized in the liver, the carcinogenic potential of acrylamide and furan in this organ is still controversial, based on findings from experimental animal studies. With the ultimate goal of providing further insights into this issue, we explored in vitro, using a hepatocyte cell line and a hepatocellular carcinoma cell line, the putative effect of these metabolites as carcinogens and cancer promoters. Molecular alterations were investigated in cells that survive glycidamide and BDA toxicity. We observed that those cells express CD133 stemness marker, present a high proliferative capacity and display an adjusted expression profile of genes encoding enzymes involved in oxidative stress control, such as GCL-C, GSTP1, GSTA3 and CAT. These molecular changes seem to be underlined, at least in part, by epigenetic remodeling involving histone deacetylases (HDACs). Although more studies are needed, here we present more insights towards the carcinogenic capacity of glycidamide and BDA and also point out their effect in favoring hepatocellular carcinoma progression.
KW - cis-2-Butene-1,4-dial (BDA)
KW - Glycidamide
KW - Liver cancer promotion
KW - Liver carcinogenesis
KW - Oxidative stress
UR - http://www.scopus.com/inward/record.url?scp=85132738142&partnerID=8YFLogxK
U2 - 10.1016/j.fct.2022.113251
DO - 10.1016/j.fct.2022.113251
M3 - Article
C2 - 35750087
AN - SCOPUS:85132738142
SN - 0278-6915
VL - 166
JO - Food and Chemical Toxicology
JF - Food and Chemical Toxicology
M1 - 113251
ER -