Abstract
Metabolism, DNA binding and cytopathological effects of aflatoxin B1 (AFB1) were studied in isolated tracheal explants from Syrian golden hamster. Explants were exposed to 0.1, 0.5 and 1.0 μM [14C]AFB1 in Dulbecco's modified Eagle medium for 24 h, then analyzed for AFB1-DNA binding and AFB1 metabolism. Binding (pmol AFB1/mg DNA) was dose-related (16.3 ± 1.9 to 180.8 ± 16.1) and analysis of the culture medium revealed the metabolic conversion products aflatoxicol (AFL) and aflatoxin Q1 (AFQ1). Ultrastructural analysis of sections of tracheal epithelium revealed degenerative changes primarily in the non-ciliated epithelial cells. Autoradiographic analysis of the same treated explants, however, showed no discernible distribution of label with respect to either cell type or cell location, with the exception of increased grain densities overlying vacuoles containing dark droplets. In addition, S9 prepared from hamster trachea was shown to activate AFB1 to mutagens detectable by Salmonella typhimurium TA 98, but was approximately 70 times less active on a per mg protein basis than was S9 prepared from hamster liver. These results demonstrate the metabolic capabilities of tracheal epithelial cells in the activation of AFB1, thus indicating that AFB1 present in respiratory particles may be activated by pulmonary mixed-function oxidases, posing a hazard to those exposed.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 117-130 |
| Number of pages | 14 |
| Journal | Toxicology |
| Volume | 32 |
| Issue number | 2 |
| DOIs | |
| State | Published - 1984 |
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Keywords
- Aflatoxin B
- Covalent binding
- Metabolic activation
- Tracheal explant culture
- Ultrastructural changes
ASJC Scopus subject areas
- Toxicology
Cite this
Metabolism, DNA binding, and cytotoxicity of aflatoxin B1 in tracheal explants from Syrian hamster. / Coulombe, Roger A.; Wilson, Dennis W; Hsieh, Dennis P H.
In: Toxicology, Vol. 32, No. 2, 1984, p. 117-130.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Metabolism, DNA binding, and cytotoxicity of aflatoxin B1 in tracheal explants from Syrian hamster
AU - Coulombe, Roger A.
AU - Wilson, Dennis W
AU - Hsieh, Dennis P H
PY - 1984
Y1 - 1984
N2 - Metabolism, DNA binding and cytopathological effects of aflatoxin B1 (AFB1) were studied in isolated tracheal explants from Syrian golden hamster. Explants were exposed to 0.1, 0.5 and 1.0 μM [14C]AFB1 in Dulbecco's modified Eagle medium for 24 h, then analyzed for AFB1-DNA binding and AFB1 metabolism. Binding (pmol AFB1/mg DNA) was dose-related (16.3 ± 1.9 to 180.8 ± 16.1) and analysis of the culture medium revealed the metabolic conversion products aflatoxicol (AFL) and aflatoxin Q1 (AFQ1). Ultrastructural analysis of sections of tracheal epithelium revealed degenerative changes primarily in the non-ciliated epithelial cells. Autoradiographic analysis of the same treated explants, however, showed no discernible distribution of label with respect to either cell type or cell location, with the exception of increased grain densities overlying vacuoles containing dark droplets. In addition, S9 prepared from hamster trachea was shown to activate AFB1 to mutagens detectable by Salmonella typhimurium TA 98, but was approximately 70 times less active on a per mg protein basis than was S9 prepared from hamster liver. These results demonstrate the metabolic capabilities of tracheal epithelial cells in the activation of AFB1, thus indicating that AFB1 present in respiratory particles may be activated by pulmonary mixed-function oxidases, posing a hazard to those exposed.
AB - Metabolism, DNA binding and cytopathological effects of aflatoxin B1 (AFB1) were studied in isolated tracheal explants from Syrian golden hamster. Explants were exposed to 0.1, 0.5 and 1.0 μM [14C]AFB1 in Dulbecco's modified Eagle medium for 24 h, then analyzed for AFB1-DNA binding and AFB1 metabolism. Binding (pmol AFB1/mg DNA) was dose-related (16.3 ± 1.9 to 180.8 ± 16.1) and analysis of the culture medium revealed the metabolic conversion products aflatoxicol (AFL) and aflatoxin Q1 (AFQ1). Ultrastructural analysis of sections of tracheal epithelium revealed degenerative changes primarily in the non-ciliated epithelial cells. Autoradiographic analysis of the same treated explants, however, showed no discernible distribution of label with respect to either cell type or cell location, with the exception of increased grain densities overlying vacuoles containing dark droplets. In addition, S9 prepared from hamster trachea was shown to activate AFB1 to mutagens detectable by Salmonella typhimurium TA 98, but was approximately 70 times less active on a per mg protein basis than was S9 prepared from hamster liver. These results demonstrate the metabolic capabilities of tracheal epithelial cells in the activation of AFB1, thus indicating that AFB1 present in respiratory particles may be activated by pulmonary mixed-function oxidases, posing a hazard to those exposed.
KW - Aflatoxin B
KW - Covalent binding
KW - Metabolic activation
KW - Tracheal explant culture
KW - Ultrastructural changes
UR - http://www.scopus.com/inward/record.url?scp=0021244144&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0021244144&partnerID=8YFLogxK
U2 - 10.1016/0300-483X(84)90131-8
DO - 10.1016/0300-483X(84)90131-8
M3 - Article
C2 - 6431642
AN - SCOPUS:0021244144
VL - 32
SP - 117
EP - 130
JO - Toxicology
JF - Toxicology
SN - 0300-483X
IS - 2
ER -