Activation and Specificity of Aflatoxin B 1 Binding on hhc M , a Human Oncogene of Low Efficiency, and Cell Transformation

  title={Activation and Specificity of Aflatoxin B 1 Binding on hhc M , a Human Oncogene of Low Efficiency, and Cell Transformation},
  author={STRINGNER S. Yang and Ke Zhang and George C. Yang and Janet Taub},
Aflatoxin B1 (AFB1), a metabolite of Aspergillus flavus, chemically classified as a furocoumarin, is known to be the most potent hepatocarcinogen experimentally tested in various species including trout, rat, hamster, dog and rhesus monkey.13,21 The carcinogenic effect resides in the mutagenic potential of AFB1 upon metabolic conversion into the epoxide form by liver mixed function oxidases. By mode of nucleophilic attack, AFB1-epoxide binds to DNA forming covalent bonds with the N7 of… 


Dose dependency of aflatoxin B1 binding on human high molecular weight DNA in the activation of proto-oncogene.
Excessive AFB1 binding on the hHC and PLC HMW DNAs resulted in an "over-kill" of both cell transformation capability and templating activity of the DNA.
Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver.
Quantitative studies of formation of the principal covalent product formed in liver DNA of rats treated with AFB1 proved that the major adduct formed between DNA and AFB1 in vivo is identical to that produced in vitro when AFB1 is incubated with DNA in the presence of a rat liver microsomal activating system.
Excretion of an aflatoxin-guanine adduct in the urine of aflatoxin B1-treated rats.
Spectral and chemical analysis of microgram quantities of this compound provided strong evidence that this compound is identical to authentic adduct, and measurement of this adduct in the urine of rats given injections of different doses of AFB1 showed that excretion occurs in a dose-dependent manner.
Transforming DNA sequences of human hepatocellular carcinomas, their distribution and relationship with hepatitis B virus sequence in human hepatomas.
The results suggest that HBV contributes to hepatocarcinogenesis probably via an activation mechanism involving possibly an integration or transient interaction of HBV DNA with hepatocyte DNA sequences, leading to recombination and eventual amplifications of the hhcM sequence in Mahlavu.
Searches for ultimate chemical carcinogens and their reactions with cellular macromolecules
Current data are consistent with the idea that the initiation step of chemical carcinogenesis is a mutagenic event and is caused by alteration of DNA by the ultimate carcinogens and there appears to be no requirement that they be electrophilic.
Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change
The H-ras-1 gene cloned from T24 DNA induces transformation in NIH 3T3 cells, while the same gene cloning from normal cellular DNA does not, and the functionally significant difference appears to be a single base mutation.
Fibroblast immortality is a prerequisite for transformation by EJ c-Ha-ras oncogene
It is shown that EJ c-Ha-ras-1 lacks complete transforming activity when transfected into normal fibroblasts which have a limited life-span, but can fully transform fibro Blasts that have been newly ‘immortalized’ by carcinogens.
Activation of the transforming potential of a normal cell sequence: a molecular model for oncogenesis.
The activation of the transforming potential of c-mos by the proviral LTR suggests a model whereby LTR-like elements could activate other normal cell sequences with oncogenic potential.
Mechanisms of chemical carcinogenesis
Knowledge of the mechanisms of carcinogens by chemicals provides a useful basis for approaches to the prevention of human cancer.