Hexavalent chromium increases the metabolism and genotoxicity of aromatic amine carcinogens 4-aminobiphenyl and β-naphthylamine in immortalized human lung epithelial cells.
4-Aminobiphenyl
CYP1A1
Carcinogenesis
Chromium
Genotoxicity
Lung cancer
N-Acetyltransferase 1
β-Naphthylamine
Journal
Toxicology and applied pharmacology
ISSN: 1096-0333
Titre abrégé: Toxicol Appl Pharmacol
Pays: United States
ID NLM: 0416575
Informations de publication
Date de publication:
15 08 2022
15 08 2022
Historique:
received:
23
03
2022
revised:
18
05
2022
accepted:
28
05
2022
pubmed:
7
6
2022
medline:
14
7
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
Humans are exposed to carcinogenic chemicals via occupational and environmental exposures. Common chemicals of concern that can occur in exposures together are aromatic amines (e.g., 4-aminobiphenyl [4-ABP] and β-naphthylamine [BNA]) and hexavalent chromium (Cr[VI]). Arylamine N-acetyltransferases 1 and 2 (NAT1 and NAT2) are key to the metabolism of aromatic amines and their genotoxicity. The effects of Cr(VI) on the metabolism of aromatic amines remains unknown as well as how it may affect their ensuing toxicity. The objective of the research presented here is to investigate the effects of Cr(VI) on the metabolism and genotoxicity of 4-ABP and BNA in immortalized human lung epithelial cells (BEP2D) expressing NAT1 and NAT2. Exposure to Cr(VI) for 48 h increased NAT1 activity (linear regression analysis: P < 0.0001) as measured by N-acetylation of para-aminobenzoic acid (PABA) in BEP2D cells but not NAT2 N-acetylation of sulfamethazine, which are prototypic NAT1 and NAT2 substrates respectively. Cr(VI) also increased the N-acetylation of 4-ABP and BNA. In BEP2D cells the N-acetylation of 4-ABP (1-3 μM) exhibited a dose-dependent increase (linear regression analysis: P < 0.05) following co-incubation with 0-3 μM Cr(VI). In BEP2D cells, incubation with Cr(VI) caused dose-dependent increases (linear regression analysis: P < 0.01) in expression of CYP1A1 protein and catalytic activity. For genotoxicity, BEP2D cells were exposed to 4-ABP or BNA with/without Cr(VI) for 48 h. We observed dose-dependent increases (linear regression analysis: P < 0.01) in phospho-γH2AX protein expression for combined treatment of 4-ABP or BNA with Cr(VI). Further using a CYP1A1 inhibitor (α-naphthoflavone) and NAT1 siRNA, we found that CYP1A1 inhibition did not reduce the increased N-acetylation or genotoxicity of BNA by Cr(VI), while NAT1 inhibition did reduce increases in BNA N-acetylation and genotoxicity by Cr(VI). We conclude that during co-exposure of aromatic amines and Cr(VI) in human lung cells, Cr(VI) increased NAT1 activity contributing to increased 4-ABP and BNA genotoxicity.
Identifiants
pubmed: 35662664
pii: S0041-008X(22)00240-X
doi: 10.1016/j.taap.2022.116095
pmc: PMC9382885
mid: NIHMS1823279
pii:
doi:
Substances chimiques
Amines
0
Aminobiphenyl Compounds
0
Carcinogens
0
Isoenzymes
0
Chromium
0R0008Q3JB
4-biphenylamine
16054949HJ
chromium hexavalent ion
18540-29-9
2-Naphthylamine
CKR7XL41N4
Cytochrome P-450 CYP1A1
EC 1.14.14.1
Acetyltransferases
EC 2.3.1.-
Arylamine N-Acetyltransferase
EC 2.3.1.5
NAT2 protein, human
EC 2.3.1.5
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
116095Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES030283
Pays : United States
Organisme : NIEHS NIH HHS
ID : P42 ES023716
Pays : United States
Organisme : NCI NIH HHS
ID : R25 CA134283
Pays : United States
Organisme : NIEHS NIH HHS
ID : T32 ES011564
Pays : United States
Informations de copyright
Copyright © 2022 Elsevier Inc. All rights reserved.
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