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Carcinogenesis Advance Access published online on October 24, 2003
Carcinogenesis, doi:10.1093/carcin/bgg199
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CANCER BIOLOGY

Effect of arsenic on benzo[a]pyrene DNA adduct levels in mouse skin and lung

C. D. Evans 1, K. LaDow 1, B. L. Schumann 1, R. E. Savage Jr2, J. Caruso 3, A. Vonderheide 3, P. Succop 1, and G. Talaska 1*

1 University of Cincinnati, Department of Environmental Health, 3223 Eden Ave., Cincinnati, OH, 45267-0056
2 NIRS,EPHB,DART,NIOSH, 4676 Columbia Parkway, Cincinnati, OH 45226-1998
3 University of Cincinnati, Department of Chemistry, 137 McMicken, Cincinnati, OH, 45267-0037

* Corresponding author. E-mail: TALASKGG{at}UCMAIL.UC.EDU.

Received 13 June 2003 ; revised 6 October 2003 ; accepted 12 October 2003

Abstract

Concomitant exposures to arsenic and polycyclic aromatic hydrocarbons (PAHs) such as benzo[a]pyrene (BaP) are widespread. While BaP acts by binding to and inducing mutations in critical sites on DNA, the mechanism(s) of arsenic carcinogenesis remains unknown. Data from epidemiological studies of arsenic copper smelter workers and arsenic ingestion in drinking water suggest a positive interaction for arsenic exposure and smoking and lung cancer. A previous in vitro study showed that arsenic potentiated the formation of DNA adducts at low doses of BaP and arsenic. The present study was conducted to test the effect of arsenic on BaP DNA adduct formation in vivo.

We hypothesized that arsenic co-treatment would significantly increase BaP adduct levels in C57BL/6 mouse target organs: skin and lung. Treatment groups were, 5 mice: -BaP/-Arsenic; 5 mice: -BaP/+Arsenic; 15 mice: +BaP/-Arsenic; 15 mice: +BaP/+Arsenic. Mice in the appropriate groups were provided sodium arsenite in drinking water (2.1 mg/l), ad libitum, for 13 days (starting 9 days before BaP treatment), and 200 nanomoles BaP/25 µl acetone (or acetone alone) was applied topically, once/day for 4 days. DNA was extracted from skin and lung and assayed by 32P-postlabelling. Statistical comparisons were made using independent t-tests (unequal variances assumed).

BaP-DNA adduct levels in the +BaP groups were significantly higher than -BaP controls. Arsenic co-treatment increased average BaP adduct levels in both lung and skin; the increase was statistically significant in the lung (P = 0.038). BaP adduct levels in the skin of individual animals were positively related to skin arsenic concentrations. These results corroborate our in vitro findings and provide a tentative explanation for arsenic and PAHs interactions in lung carcinogenesis.


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