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THE EFFECT OF ROUTE OF ADMINISTRATION OF POLYCYCLIC AROMATIC HYDROCARBONS ON DNA ADDUCTION AND CYTOGENETIC DAMAGE IN PERIPHERAL BLOOD LYMPHOCYTES OF MICE AND RATS
Citation:
Kligerman, A D., G. L. Erexson, G B. Nelson, AND J A. Ross. THE EFFECT OF ROUTE OF ADMINISTRATION OF POLYCYCLIC AROMATIC HYDROCARBONS ON DNA ADDUCTION AND CYTOGENETIC DAMAGE IN PERIPHERAL BLOOD LYMPHOCYTES OF MICE AND RATS. Presented at ISPAC 18, Cincinnati, Ohio, 09/09-13/01.
Description:
The effect of route of administration of polycyclic aromatic hydrocarbons on DNA adduction and cytogenetic damage in peripheral blood lymphocytes of mice and rats
Experiments were designed to investigate how the route of exposure to polycyclic
aromatic hydrocarbons (PARs) in mice and rats affects cytogenetic endpoints and DNA adduction and to determine the relationship between the induction of cytogenetic damage and DNA adduction. Both mice and rats were exposed to 100 mg/kg of one of four PAHs --benz[a]anthracene (B[a]A), benzo[b]fluoranthene (B[b]F), benzo[a]pyrene (B[a]P), or chrysene (CRR)-- by gavage or by intraperitoneal injection (ip.). Peripheral blood lymphocytes (PBLs) were removed by cardiac puncture 7 days after PAR administration. Samples of blood were divided, and one sample was cultured fqr examination of the sister chromatid exchange (SCE) frequency and the frequency of micronuclei (mouse only) in cytochalasin B-induced binucleate cells (MNBN). The matching sample was analyzed for DNA adduction using 32p postlabeling. DNA adduction was found in the lymphocytes of all animals with each P AH. The ip. route of exposure produced the most cytogenetic damage and DNA adduction. For the mouse, the order of potency for SCE induction was: B[b]F=B[a]P>B[a]A>CRR on either a mg/kg or mmole/kg basis. Only B[a]P induced a significant increase in MNBN. With gavage administration, oniy B[a]P and B[a]A induced a significant increase in SCEs, with B[a]P . being the more potent. B[a]P also induced a small significant increase in MNBN. In the rat only B[a]P and B[b]F induced a significant increase in SCE by either route of exposure, with B[a]P being the more potent. Overall, the mouse was more sensitive than the rat as measured by either SCE induction or the total amount of DNA adducts/ug DNA. Of the four PAHs examined, B[a]P was the most potent as measured by DNA adduction and cytogenetic damage. In general, there was a significant correlation between the ability of a chemical to induce cytogenetic damage and to produce DNA adducts.
This abstract does not represent EPA policy.