| Description: |
Aflatoxin G1 (AFG1 ), a member of the AF family with cytotoxic and carcinogenic properties, could cause DNA damage in alveolar type II (AT-II) cells and induce lung adenocarcinoma. AFG1 induces TNF-α-dependent lung inflammation, which upregulates CYP2A13 to promote the metabolic activation of AFG1 and enhance oxidative DNA damage in AT-II cells. Dillapiol as a specific inhibitor of aflatoxin G1 production, it inhibited aflatoxin G1 production by Aspergillus parasiticus with an IC50 value of 0.15 microM. |
| Targets: |
TNF-α | NF-κB | CYP2A13 |
| In vitro: |
| Canadian Journal of Microbiology, 1967, 13(6):629. | | Aflatoxin G1 uptake by cells of Flavobacterium aurantiacum.[Reference: WebLink] |
METHODS AND RESULTS:
Aflatoxin G1 was removed from liquid cultures by growing and resting cells of Flavobacterium aurantiacum NRRL B-184. In inoculated culture media containing toxin levels of 7.5 p.p.m. and above, there was a protracted growth lag which was subsequently overcome; toxin removal then occurred, concomitant with growth. Only a few cells demonstrated aberrant morphological forms when cultured in the presence of aflatoxin G1. A comparison of the effects of aflatoxin G1 with B1 on growth and morphology showed that B1 was distinctly more toxic.
CONCLUSIONS:
Three hundred and thirty micrograms of aflatoxin G1 was removed per 1 × 1013 resting cells during a 4-hour incubation period. Preincubation of resting cells with aflatoxin B1 did not interfere with subsequent uptake of G1. | | Biosci Biotechnol Biochem. 2007 Sep;71(9):2329-32. | | Dillapiol and Apiol as specific inhibitors of the biosynthesis of aflatoxin G1 in Aspergillus parasiticus.[Pubmed: 17827697 ] |
METHODS AND RESULTS:
Dillapiol was isolated from the essential oil of dill as a specific inhibitor of aflatoxin G1 production. It inhibited aflatoxin G1 production by Aspergillus parasiticus with an IC50 value of 0.15 microM without inhibiting aflatoxin B1 production or fungal growth. Apiol and myristicin, congeners of dillapiol, showed similar activity with IC50 values of 0.24 and 3.5 microM, respectively. |
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| In vivo: |
| J Cell Physiol. 2019 Jun;234(6):9194-9206. | | Aflatoxin G1 induced TNF-α-dependent lung inflammation to enhance DNA damage in alveolar epithelial cells.[Pubmed: 30478833] | Aflatoxin G1 (AFG1 ), a member of the AF family with cytotoxic and carcinogenic properties, could cause DNA damage in alveolar type II (AT-II) cells and induce lung adenocarcinoma. Recently, we found AFG1 could induce chronic lung inflammation associated with oxidative stress in the protumor stage. Chronic inflammation plays a critical role in cigarette smoke or benzo[a]pyrene-induced lung tissues damage. However, it is unclear whether and how AFG1 -induced lung inflammation affects DNA damage in AT-II cells.
METHODS AND RESULTS:
In this study, we found increased DNA damage and cytochrome P450 (CYP2A13) expression in AFG1 -induced inflamed lung tissues. Furthermore, we treated the mice with a soluble tumor necrosis factor (TNF)-α receptor and AFG1 and found that TNF-α neutralization inhibited the AFG1 -induced chronic lung inflammation in vivo, and then reversed the CYP2A13 expression and DNA damage in AT-II cells. The results suggest that AFG1 induces TNF-α-dependent lung inflammation to regulate 2A13 expression and enhance DNA damage in AT-II cells. Then, we treated the primary mice AT-II cells and human AT-II like cells (A549) with AFG1 and TNF-α and found that TNF-α enhanced the AFG1 -induced DNA damage in mice AT-II cells as well as A549 cells in vitro. In AFG1 -exposed A549 cells, TNF-α-enhanced DNA damage and apoptosis were reversed by CYP2A13 small interfering RNA. Blocking NF-κB pathway inhibited the TNF-α-enhanced CYP2A13 upregulation and DNA damage confirming that the CYP2A13 upregulation by TNF-α plays an essential role in the activation of AFG1 under inflammatory conditions.
CONCLUSIONS:
Taken together, our findings suggest that AFG1 induces TNF-α-dependent lung inflammation, which upregulates CYP2A13 to promote the metabolic activation of AFG1 and enhance oxidative DNA damage in AT-II cells. |
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