You are here:
DOSE-RESPONSE RELATIONSHIPS FOR MOLECULAR ALTERATIONS INDUCED BY B[ A ]P IN STRAIN A/J MOUSE LUNG
Citation:
ROSS, J. A., G. B. NELSON, S. NESNOW, AND S. Y. THAI. DOSE-RESPONSE RELATIONSHIPS FOR MOLECULAR ALTERATIONS INDUCED BY B[ A ]P IN STRAIN A/J MOUSE LUNG. Presented at 21st International Symposium for Polycyclic Aromatic Compounds (ISPAC), Trondheim, NORWAY, August 05 - 10, 2007.
Description:
Benzo[a]pyrene (B[a]P) induces tumors in rodents at doses much higher than those found in the environment. Current cancer risk assessment of B[a]P assumes that the risk posed by low level exposure to B[a]P is linear with respect to dose. We have measured the dose response relationships for several putative key molecular events in carcinogenesis in the lungs of strain A/J mice after administration of low doses of B[a]P. We identified genes whose expression was significantly altered by administration of 50 mg/kg B[a]P using Affymetrix microarray expression analysis. The expression of these genes in mouse lung was then measured by quantitative real time PCR and compared to expression in untreated control animals at one and three days after administration of doses of 50, 5, or 0.5 mg/kg B[a]P. Expression of Cyp1a1 and Cyp1b1 was induced in a non-linear manner by B[a]P, as was expression of the Ahr repressor, the Kit oncogene, Bteb, Stmn2, and Ccbp2. Formation of stable covalent DNA adducts in mouse lungs was determined by 32P-postlabeling analysis at 1, 3, 7, and 21 days after B[a]P administration at doses of 5, 0.5, 0.05, 0.01, and 0 mg/kg. The DNA adducts formed at the low doses of
B[a]P were produced at levels lower than those predicted by a linear model, with no adducts detectable at either the 0.05 or 0.01 mg/kg doses. The failure to detect adducts at these low doses is not due to lack of sensitivity of the postlabeling assay.