Metabolism of Aflatoxin B1and Identification of the Major Aflatoxin B1-DNA Adducts Formed in Cultured Human Bronchus and Colon1

Aflatoxin B, and benzo(a)pyrene were activated by both cultured human bronchus and human colon as measured by binding to cellular DNA and protein. The binding of aflatoxin B, to DNA was dose dependent, and the level of binding was higher in cultured human bronchus than it was in the colon. When compared to aflatoxin B,, the binding level of benzo(a)pyrene to both bronchial and colonic DNA was generally higher. The major adducts formed in both tissues by the interaction of aflatoxin B1 and DNA were chromatographically identical to 2,3-dihydro-2-(N7-guanyl)3-hydroxyaflatoxin B, (Structure I) with the guanyl group and hydroxy group in trans-position and an adduct which has been tentatively identified by other investigators as 2,3dihydro-2-(N5-formyl-2' ,5' ,6'-tniamino-4'-oxo-N5-pyrimidyl)3-hydroxyaflatoxin B, (Structure II). Seventy % of the radio activity associated with bronchial DNA was found in these two peaks, and the ratio of radioactivity between the peaks was nearly 1. In colonic DNA, the ratio between Structures I and II was approximately 2. These observations add aflatoxin B, to the list of chemical procarcinogens metabo lized by cultured human tissues and in which the carcino gen-DNA adducts are similar to the adducts formed in animal tissue susceptible to the carcinogenic action of aflatoxin B1.

[1]  C. Harris,et al.  Metabolism of benzo(a)pyrene and identification of the major benzo(a)pyrene-DNA adducts in cultured human colon. , 1978, Cancer research.

[2]  J. Vaught,et al.  Association and dissociation of the Ah locus with the metabolism of aflatoxin B1 by mouse liver. Co-segregation of aflatoxin B1 hydroxylase induction with aryl hydrocarbon (benzo(a)pyrene) hydroxylase induction. , 1978, The Journal of biological chemistry.

[3]  B. Paigen,et al.  Metabolic activation of aflatoxins related to their mutagenicity. , 1978, Biochemical and biophysical research communications.

[4]  J. Essigmann,et al.  Identification of the principal aflatoxin B1-DNA adduct formed in vivo in rat liver. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[5]  R. Harvey,et al.  The reaction of trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydrobenzo(a)pyrene with DNA involves attack at the N7-position of guanine moieties. , 1978, Chemico-biological interactions.

[6]  D. Hsieh,et al.  Aflatoxicol: major aflatoxin B1 metabolite in rat plasma. , 1978, Science.

[7]  C. Harris,et al.  Explant culture of human colon. , 1978, Gastroenterology.

[8]  C. Harris,et al.  Metabolism of acyclic and cyclic N-nitrosamines in cultured human bronchi. , 1977, Journal of the National Cancer Institute.

[9]  P. Newberne,et al.  Preventive role of vitamin a in colon carcinogenesis in rats , 1977, Cancer.

[10]  S. Luria,et al.  Effects of diet on conversion of aflatoxin B1 to bacterial mutagen(s) by rats in vivo and by rat hepatic microsomes in vitro , 1977 .

[11]  R. T. Jones,et al.  Metabolism of benzo[a]pyrene and 7,12-dimethylbenz[a]anthracene in cultured human bronchus and pancreatic duct. , 1977, Cancer research.

[12]  C. Harris,et al.  Structures of benzo(a)pyrene–nucleic acid adducts formed in human and bovine bronchial explants , 1977, Nature.

[13]  C. Harris,et al.  Binding of Chemical Carcinogens to Macromolecules in Cultured Human Colon: Brief Communication , 1977 .

[14]  P. Hanawalt,et al.  Repair of DNA in human cells after treatment with activated aflatoxin B1. , 1977, Cancer research.

[15]  R. C. Garner,et al.  Aflatoxin B-oxide generated by chemical or enzymic oxidation of aflatoxin B1 causes guanine substitution in nucleic acids , 1977, Nature.

[16]  J. Essigmann,et al.  Structural identification of the major DNA adduct formed by aflatoxin B1 in vitro. , 1977, Proceedings of the National Academy of Sciences of the United States of America.

[17]  C. Heidelberger,et al.  Liver homogenate-mediated mutagenesis in chinese hamster V79 cells by polycyclic aromatic hydrocarbons and aflatoxins. , 1977, Mutation research.

[18]  J. Vaught,et al.  In vitro metabolism of aflatoxin B1 by rat liver nuclei. , 1977, Life sciences.

[19]  J. Miller,et al.  Aflatoxin B1-2,3-oxide as a probable intermediate in the covalent binding of aflatoxins B1 and B2 to rat liver DNA and ribosomal RNA in vivo. , 1977, Cancer research.

[20]  D. Hsieh,et al.  Mutagenicity of aflatoxins related to their metabolism and carcinogenic potential. , 1976, Proceedings of the National Academy of Sciences of the United States of America.

[21]  I. Dvořáčková.  Aflatoxin inhalation and alveolar cell carcinoma. , 1976, British medical journal.

[22]  C. Harris,et al.  Binding of (3H)benzo(a)pyrene to DNA in cultured human bronchus. , 1976, Cancer research.

[23]  C. Linsell,et al.  Dietary aflatoxins and human liver cancer. A study in Swaziland , 1976, International journal of cancer.

[24]  T. Campbell,et al.  The role of aflatoxin metabolism in its toxic lesion. , 1976, Toxicology and applied pharmacology.

[25]  G. Deger.  Letter: Aflatoxin--human colon carcinogenesis? , 1976, Annals of internal medicine.

[26]  C. Harris.  Chemical carcinogenesis and experimental models using human tissues. , 1976, Beitrage zur Pathologie.

[27]  J. Ward,et al.  Effect of lifetime exposure to aflatoxin b1 in rats. , 1975, Journal of the National Cancer Institute.

[28]  R. Krieger,et al.  Aflaxation B1 hydroxylation by hepatic microsomal preparations from the rhesus monkey. , 1975, Food and cosmetics toxicology.

[29]  H. Gurtoo,et al.  Hepatic microsomal mixed function oxygenase: enzyme multiplicity for the metabolism of carcinogens to DNA-binding metabolites. , 1974, Biochemical and biophysical research communications.

[30]  H. Yoshino,et al.  Substrate Specificity of Nuclease P1 , 1974 .

[31]  C. Harris,et al.  Studies of Ultrastructure, Cytochemistry, and Organ Culture of Human Bronchial Epithelium , 1974 .

[32]  T. Campbell,et al.  Preliminary study of in vitro aflatoxin B 1 metabolism by human liver. , 1974, Toxicology and applied pharmacology.

[33]  H. Boren,et al.  Quantitative light microscopic autoradiography. , 1974, Methods in cell biology.

[34]  R. Garner.  Chemical evidence for the formation of a reactive aflatoxin B1 metabolite, by hamster liver microsomes , 1973, FEBS letters.

[35]  J. Miller,et al.  2,3-Dihydro-2,3-dihydroxy-aflatoxin B1: an acid hydrolysis product of an RNA-aflatoxin B1 adduct formed by hamster and rat liver microsomes in vitro. , 1973, Biochemical and biophysical research communications.

[36]  C. Linsell,et al.  Dietary aflatoxins and liver cancer--a population based study in Kenya. , 1973, British Journal of Cancer.

[37]  A. E. Rogers,et al.  Rat colon carcinomas associated with aflatoxin and marginal vitamin A. , 1973, Journal of the National Cancer Institute.

[38]  J. Miller,et al.  Liver microsomal metabolism of aflatoxin B 1 to a reactive derivative toxic to Salmonella typhimurium TA 1530. , 1972, Cancer research.

[39]  R. C. Shank,et al.  Dietary aflatoxins and human liver cancer. III. Field survey of rural Thai families for ingested aflatoxins , 1972 .