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Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon.

Publication ,  Journal Article
Autrup, H; Schwartz, RD; Essigmann, JM; Smith, L; Trump, BF; Harris, CC
Published in: Teratog Carcinog Mutagen
1980

A model system for comparing carcinogen metabolism between human and rat colon has been developed. Tissue explants maintained under chemically defined conditions were treated with radioactively labeled carcinogens. After incubation for 24 hours, the binding of radioactive carcinogen to DNA was quantitated. Further, the carcinogen-DNA adducts and carcinogen metabolites released into the culture media were identified. Both human and rat colon activate benzo[a]pyrene (BP), aflatoxin B1 (AFB), and 1,2-dimethylhydrazine (DMH) into chemical species that reacted with cellular macromolecules. When human and rat colons were compared, the metabolism of AFB and DMH was qualitatively similar - the same major carcinogen-DNA adducts and metabolic profile. However, the mean binding levels of DMH and AFB to colonic DNA were higher in rats than in humans. BP-guanine adducts were the major adducts formed by both rat and human colonic DNA. However, BP-adenine adducts were observed in rat colonic DNA but not in human colonic DNA. A positive correlation for the binding of BP and DMH to human DNA of different individuals was observed, but no correlation was found between BP and AFB. The data suggest that similar enzyme systems may be involved in the metabolism of BP and DMH, whereas different enzymes might be involved in the metabolic activation of AFB.

Duke Scholars

Published In

Teratog Carcinog Mutagen

DOI

ISSN

0270-3211

Publication Date

1980

Volume

1

Issue

1

Start / End Page

3 / 13

Location

United States

Related Subject Headings

  • Toxicology
  • Rats
  • Organ Culture Techniques
  • Methylhydrazines
  • Male
  • Humans
  • Dimethylhydrazines
  • DNA
  • Colon
  • Carcinogens
 

Citation

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Autrup, H., Schwartz, R. D., Essigmann, J. M., Smith, L., Trump, B. F., & Harris, C. C. (1980). Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon. Teratog Carcinog Mutagen, 1(1), 3–13. https://doi.org/10.1002/tcm.1770010103
Autrup, H., R. D. Schwartz, J. M. Essigmann, L. Smith, B. F. Trump, and C. C. Harris. “Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon.Teratog Carcinog Mutagen 1, no. 1 (1980): 3–13. https://doi.org/10.1002/tcm.1770010103.
Autrup H, Schwartz RD, Essigmann JM, Smith L, Trump BF, Harris CC. Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon. Teratog Carcinog Mutagen. 1980;1(1):3–13.
Autrup, H., et al. “Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon.Teratog Carcinog Mutagen, vol. 1, no. 1, 1980, pp. 3–13. Pubmed, doi:10.1002/tcm.1770010103.
Autrup H, Schwartz RD, Essigmann JM, Smith L, Trump BF, Harris CC. Metabolism of aflatoxin B1, benzo[a]pyrene, and 1,2-dimethylhydrazine by cultured rat and human colon. Teratog Carcinog Mutagen. 1980;1(1):3–13.

Published In

Teratog Carcinog Mutagen

DOI

ISSN

0270-3211

Publication Date

1980

Volume

1

Issue

1

Start / End Page

3 / 13

Location

United States

Related Subject Headings

  • Toxicology
  • Rats
  • Organ Culture Techniques
  • Methylhydrazines
  • Male
  • Humans
  • Dimethylhydrazines
  • DNA
  • Colon
  • Carcinogens