Contribution of the glutathione S-transferases to the mechanisms of resistance to aflatoxin B1.
The harmful effects of Aflatoxin B1 (AFB1) are a consequence of it being metabolized to AFB1-8,9-epoxide, a compound that serves as an alkylating agent and mutagen. The toxicity of AFB1 towards different cells varies substantially; sensitivity can change significantly during development, can be modulated by treatment with xenobiotics and is decreased markedly in preneoplastic lesions as well as in tumors. Three types of resistance, namely intrinsic, inducible and acquired, can be identified. The potential resistance mechanisms include low capacity to form AFB1-8,9-epoxide, high detoxification activity, increase in AFB1 efflux from cells and high DNA repair capacity. Circumstantial evidence exists that amongst these mechanisms the glutathione S-transferases, through their ability to detoxify AFB1-8,9-epoxide, play a major role in determining the sensitivity of cells to AFB1.
Hayes
J D
JD
University Department of Clinical Chemistry, Royal Infirmary, Edinburgh, Scotland, U.K.
Judah
D J
DJ
McLellan
L I
LI
Neal
G E
GE
D016604:Aflatoxin B1 / Q000031:analogs & derivatives / Q000378:metabolism / Q000633:toxicity*; D000595:Amino Acid Sequence; D000818:Animals; D004351:Drug Resistance / Q000502:physiology; D005982:Glutathione Transferase / Q000502:physiology*; D006801:Humans; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008969:Molecular Sequence Data; D013045:Species Specificity
C006426:aflatoxin B1-2,3-oxide; D016604:Aflatoxin B1; D005982:Glutathione Transferase