Model | PM type | Dose and application | Exposure time | Main findings | Ref. |
---|---|---|---|---|---|
Ex vivo human skin | SRM® 1649b | 2 mg/cm2, topical | 24 h | - Lipid peroxidation. | [119] |
Mice, C-57 | Diesel PM | 4.5, 11.1 and 26.7 mg/cm2, topical | 80 h | - Increased DNA adduct formation. | [166] |
Mice, FVB/N | SRM® 1650b | 1 mg/time (PAH extracted), topical | 12 h | - Increased CYP1B1 mRNA expression. | [167] |
Mice, HR-1 | SRM® 1650b | 100 μg/mL, topical | 7 d | - Increased protein carbonylation and lipid peroxidation. | [168] |
SRM® 1650b | 100 μg/mL, topical | 7 d | - ER stress: upregulation protein expression of CHOP and GRP78. - Lipid peroxidation: increased expression of HNE protein. - Mitochondrial and ER swelling. - Increased protein carbonylation. - Apoptosis: increased protein expression of BAX, active caspase-3, and caspase-9, and DNA breakage. - Autophagy: increased protein expression of LC3B-II. | [123] | |
SRM® 1650b | 100 μg/mL, topical | 7 d | - Increased protein carbonylation. - Increased NOX4 protein expression. | [169] | |
HSE | SRM® 2975 | 200 μg/mL, systemic | 2 d repetitive exposure, 6 d total | - Increased protein expression of cleaved caspase-3. | [125] |
HEE | CAPs, PM2.5 | 0.5 and 2.0 μg/cm2, topical | 24 and 48 h | - Increased isoprostanes protein level. - Increased HNE protein expression. - Increased CYP1A1 protein expression. - Increased DNA fragmentation. | [128] |
CAPs, PM2.5 | 25 μg/mL, topical | 24 and 48 h | - Increased protein carbonylation. | [170] | |
PM0.3–2.5 from Benin, West-Africa | 30 μg/cm2, topical | 24 h | - Increased HNE protein expression. - Increased HMOX1, metallothionein 1G and 1E, cyclin dependent kinase inhibitor 2A, and caspase 3 mRNA expression. - Decreased BIRC5 mRNA expression. | [133] | |
CRM no. 28 | 25 mg, topical | 6 h | - Upregulated mRNA expression of CYP1A1, CYP1B1, and SOD2. | [129] | |
SRM® 1975 | 5 mg/mL, topical | 48 h | - Increased level of carbonylated proteins | [171] | |
SRM® 1648a | 2.2, 8.9, and 17.9 μg/cm2, topical | 24 and 48 h | - Decreased AhR and increased NOTCH1 protein expression. | [131] | |
NHDF | SRM® 2787 | 30 μg/cm2, systemic | 24 h | - Autophagy: accumulation of LC3-II. - Mitochondrial stress: deformed mitochondria. - Increased CYP1A1 and CYP1B1 mRNA expression. | [135] |
ERM-CZ100 | 50–400 μg/mL, systemic | 3.3 h | - Increased levels of intracellular ROS. | [136] | |
The pre-conditioned medium of HaCaT treated with CRM no. 28 | 125 μg/mL, systemic | 30 m, 48 h post-incubation | - Increased levels of intracellular ROS. - Increased number of apoptotic bodies. | [137] | |
SRM® 1649b | 50 μg/mL, systemic | 24 h | - Increased intracellular ROS levels. - Activation of AhR (XRE activity). - Upregulation of CYP1A1 mRNA expression. | [119] | |
SRM® 1649b | 100–400 μg/mL, systemic | 24 h | - Nuclear translocation of AhR. - Increased mRNA expression of CYP1A1. - Induced apoptosis. | [172] | |
NHEK | Diesel PM or vapour | 0.05% (v/v), systemic | 20 d | - Increased Nrf2 protein expression. - Mitochondrial dysfunction: overexpression of proteins from mitochondrial complex I and IV. | [127] |
SRM® 1975 | 5 mg/mL, systemic | 1 and 24 h | - Increased intracellular ROS levels. - Increased of CYP1A1 mRNA expression. - Nuclear translocation of AhR. | [171] | |
ERM-CZ120 | 3, 10, 30 and 100 μg/mL, systemic | 24 and 48 h | - Increased ROS levels after 24 h. - Increased NOX1 and NOX2 mRNA expression after 24 h. | [173] | |
PM ≤1 μm from Seoul, Korea | 40 μg/cm2, systemic | 24 h | - Increased ROS production. - Inhibition of ROS inhibited cytokine secretion. | [121] | |
PM2.5 from Seoul, Korea | 25 μg/mL, systemic | 24 h | - Top upregulated genes from transcriptomics analysis are CYP1A1 and CYP1B1. | [132] | |
PM2.5 from Xi’an, China | 50 μg/mL, systemic | 24 h | - Top upregulated genes from transcriptomics analysis are CYP1A1 and SOD2. | [134] | |
Asian dust storm particles from Seoul, Korea | 25 μg/mL, systemic | 24 h | - Increased CYP1A1, CYP1A2, and CYP1B1 mRNA expression. | [139] | |
Diesel PM | 30 and 60 μg/mL, systemic | 24 h | - Increased ROS production. - Increased HMOX1 mRNA and protein expression. - Increased Nrf2 mRNA expression. | [138] | |
SRM® 2786 | 1 mg/mL, systemic | 6 h | - RNA-Seq analysis: Downregulation of ER stress apoptosis-related genes such as ATF4 and CHOP. No activation of BCL2, BAX, caspase 3, and caspase 8. - Upregulation of HMOX1, CYP1A1, CYP1B1, and NQO1. | [141] | |
SRM® 1650b and 2975 | 10 and 100 μg/mL, systemic | 1 and 24 h | - Increased radical production. | [174] | |
NHEK, HaCaT, and HEK001 | SRM® 1650b | 50 μg/mL, systemic | 72 h | - Induced senescence: increased β-galactosidase activity. | [124] |
NHEK and HaCaT | SRM® 1650b | 50 μg/mL, systemic | 0.5–48 h | - Increased intracellular ROS levels. - Nuclear translocation of AhR (0.5 h). - Induced senescence: upregulation of P16INK4A and increased number of SAHF/nuclei. Decreased colony-forming ability. - Senescence is AhR dependent. - Transcriptional regulation of P16INK4A correlates with DNA demethylation: lower methylation of the P16INK4A promoter region. | [124] |
NHDF and HaCaT | SRM® 1650b | 50 μg/mL, systemic | 30 m and 24 h | - Increased levels of lipid peroxidation and protein carbonylation after 24 h. - Increased levels of superoxide anion, hydroxyl radicals, and intracellular ROS (30 m). - Increased intracellular and mitochondrial calcium levels after 24 h. - Increased protein expression of CHOP, GRP78, active caspase-3, caspase-9, PARP, and BAX after 24 h. - Downregulated protein expression of Bcl-1 and Mcl-1 after 24 h. - Increased mitochondrial permeability after 24 h. - Reduced ATP levels after 24 h. - Increased DNA degradation and the number of apoptotic bodies after 24 h. | [175] |
HaCaT | PM2.5 from Bangkok, Thailand | 100 μg/mL, systemic | 30 m | - Increased intracellular ROS levels. | [176] |
PM2.5 from Taoyuan, China | 25, 50, 100 and 200 μg/mL, systemic | 24 h | - Increased intracellular ROS levels. - Decreased SOD activity. - Increased lipid peroxidation: accumulation of MDA protein. - Induced formation of apoptotic bodies. - Induced protein expression of cytochrome c, active caspase-3, and caspase-9. - DNA damage. | [177] | |
SRM® 1648a | 50–200 ppm, systemic | 24 and 48 h | - Increased ROS production. | [130] | |
SRM® 1648a SRM® 1649b | 50 μg/cm2, systemic | 24 h | - Nuclear translocation of AhR. - Increased CYP1A1 and CYP1B1 mRNA expression. | [178] | |
SRM® 1649b | 50 μg/cm2, systemic | 1 h | - Increased levels of intracellular ROS. | [142] | |
SRM® 1649b | 50 μg/cm2, systemic | 2 and 24 h | - Increased cellular and mitochondrial ROS levels after 2 h. - Increased HMOX1 protein expression after 24 h. | [143] | |
SRM® 1649b | 25 and 50 μg/cm2, systemic | 4 and 24 h | - Increased ROS production. - Increased NOX activity. | [122] | |
SRM® 1649b | 25–100 μg/cm2, systemic | 4 and 24 h | - Increased NOX2 protein expression. - Increased ROS production. | [179] | |
SRM® 1649b | 25 μg/mL, systemic | 2 and 24 h | - Increased ROS production. | [180] | |
SRM® 1649b | 50 μg/cm2, systemic | 1 and 4 h | - Increased ROS production. - Increased NOX2 activity. | [181] | |
SRM® 1649b | 25 and 50 μg/cm2, systemic | 4 and 24 h | - Increased ROS production - Increased NOX activity. | [122] | |
SRM® 1649b | 100–400 μg/mL, systemic | 24 h | - Nuclear translocation of AhR. - Increased CYP1A1 mRNA expression. - Induced apoptosis. | [172] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Increased cellular and mitochondrial ROS levels and mitochondrial stress. - Increased lipid peroxidation and protein carbonylation. - Increased cleaved caspase-3 and BAX and decreased Bcl-2 protein expression. - Induced DNA damage. - Increased number of apoptotic bodies. | [182] | |
SRM® 1650b | 50 μg/mL, systemic | 1 and 24 h | - Increased intracellular ROS and superoxide anion levels. - Increased levels of protein carbonylation and lipid peroxidation after 24 h. - Induced DNA damage and apoptotic body formation. - Increased mitochondrial permeability after 24 h. - Increased BAX, active caspase-3, and PARP and decreased Bcl-2 protein expression. | [183] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Increased intracellular ROS and calcium levels. - Increased levels of lipid peroxidation and protein carbonylation. - DNA damage. - Increased mitochondrial ROS, calcium, and permeability. - Apoptosis: increased protein expression of ATF6, GRP78, p-IRE1, BAX, and active caspase-3 and caspase-9. Decreased protein expression of Bcl2. Increased number of apoptotic bodies. - Autophagy: autophagic lysosomes. Increased protein expression of LC3B-II and beclin-1. | [168] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Increased intracellular ROS and superoxide levels. - Induced NOX activity. - Increased intracellular calcium levels and mitochondrial membrane permeability. - Induced lipid peroxidation and protein carbonylation. - DNA damage. - Increased number of apoptotic bodies. | [184] | |
SRM® 1650b | 50 μg/mL, systemic | 1, 4, 8, 12, and 24 h | - Increased intracellular ROS. - Increased levels of intracellular calcium. - ER stress: Increased protein expression of CHOP, GRP78, and p-PERK. - Increased mitochondrial permeability. - DNA damage. - Increased lipid peroxidation and protein carbonylation. - Apoptosis: Increased protein expression of BAX, DNA breakage, apoptotic body formation, and increased expression of active caspase-3 and caspase-9. - Autophagy: Increased protein expression of LC3B-II. | [123] | |
SRM® 1650b | 50 μg/mL, systemic | 30 m, 1 h, and 24 h | - Increased ROS production. - Increased levels of intracellular calcium. - Induced senescence. | [185] | |
SRM® 1650b | 50 μg/mL, systemic | 24 h | - Increased ROS production. - Increased lipid peroxidation. - Increased number of apoptotic bodies. | [186] | |
SRM® 1650b and 2975 | 10 and 100 μg/mL, systemic | 1 and 24 h | - No changes in radical production. | [174] | |
SRM® 2975 | 100 and 200 μg/mL, systemic | 24 h | - Increased protein expression of cleaved caspase-3 and PARP. - Increased protein expression of BAX and p53. | [125] | |
CRM no. 28 | 125 μg/mL, systemic | 30 m, 24 h post-incubation | - Increased levels of intracellular ROS. | [137] | |
ERM-CZ120 | 100 μg/mL, systemic | 30 m | - Increased intracellular ROS production. | [126] | |
ERM-CZ120 | 25–100 μg/mL, systemic | 3 and 24 h | - Increased CYP1A1 protein expression. - Decreased AhR protein expression. - Increased LC3-II and p62 protein expression. | [187] | |
CAPs, PM2.5 | 5–25 μg/mL, systemic | 1, 3, 6, and 24 h | - Increased HNE protein adduct formation. - Increased nuclear translocation of Nrf2. - No changes in GPX, GR, and NPQO1 mRNA expression. | [145] |