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Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels.

Publication ,  Journal Article
Ross, JA; Nelson, GB; Wilson, KH; Rabinowitz, JR; Galati, A; Stoner, GD; Nesnow, S; Mass, MJ
Published in: Cancer Res
March 1, 1995

The induction of DNA adducts and adenomas in the lungs of strain A/J mice has been investigated following the single i.p. administration of each of the following polycyclic aromatic hydrocarbons (PAH): pyrene, dibenz[a,h]anthracene, benzo[a]pyrene, benzo[b]fluoranthene, 5-methylchrysene, and cyclopenta[c,d]pyrene. DNA adducts were measured by 32P-postlabeling at times between 1 and 21 days following injection, while adenomas were counted at 240 days after treatment. Pyrene did not induce either DNA adducts or lung adenomas at any of the doses examined. Each of the remaining PAH induced both adenomas and DNA adducts in a dose-dependent manner, with dibenz[a,h]anthracene > 5-methylchrysene > cyclopenta[c,d]pyrene > benzo[a]pyrene > benzo[b]fluoranthene. DNA adducts reached maximal levels between 3 and 9 days after injection, followed by a gradual decrease. The time-integrated DNA adduct level (TIDAL) was calculated by numerically integrating the areas under the adduct persistence curves extrapolated to 240 days for each PAH at each dose level. This value represents the effective total molecular dose of PAH that was delivered to the lung DNA over the entire course of tumorigenesis. A strong correlation of lung adenoma induction with the TIDAL values was observed for each PAH. The slopes of the tumors versus TIDAL value relationships were essentially identical for 5-methylchrysene, cyclopenta[cd]pyrene, benzo[a]pyrene, and benzo[b]fluoranthene. The slope of this relationship for dibenz[a,h]anthracene was markedly greater. The essentially identical induction of adenomas as a function of TIDAL values for these PAH suggests that the formation and persistence of DNA adducts determines their carcinogenic potency.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 1, 1995

Volume

55

Issue

5

Start / End Page

1039 / 1044

Location

United States

Related Subject Headings

  • Triglycerides
  • Time Factors
  • Polycyclic Compounds
  • Phosphorus Radioisotopes
  • Oncology & Carcinogenesis
  • Mice, Inbred A
  • Mice
  • Male
  • Lung Neoplasms
  • Lung
 

Citation

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MLA
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Ross, J. A., Nelson, G. B., Wilson, K. H., Rabinowitz, J. R., Galati, A., Stoner, G. D., … Mass, M. J. (1995). Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer Res, 55(5), 1039–1044.
Ross, J. A., G. B. Nelson, K. H. Wilson, J. R. Rabinowitz, A. Galati, G. D. Stoner, S. Nesnow, and M. J. Mass. “Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels.Cancer Res 55, no. 5 (March 1, 1995): 1039–44.
Ross JA, Nelson GB, Wilson KH, Rabinowitz JR, Galati A, Stoner GD, et al. Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer Res. 1995 Mar 1;55(5):1039–44.
Ross JA, Nelson GB, Wilson KH, Rabinowitz JR, Galati A, Stoner GD, Nesnow S, Mass MJ. Adenomas induced by polycyclic aromatic hydrocarbons in strain A/J mouse lung correlate with time-integrated DNA adduct levels. Cancer Res. 1995 Mar 1;55(5):1039–1044.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

March 1, 1995

Volume

55

Issue

5

Start / End Page

1039 / 1044

Location

United States

Related Subject Headings

  • Triglycerides
  • Time Factors
  • Polycyclic Compounds
  • Phosphorus Radioisotopes
  • Oncology & Carcinogenesis
  • Mice, Inbred A
  • Mice
  • Male
  • Lung Neoplasms
  • Lung