Skip directly to search Skip directly to A to Z list Skip directly to page options Skip directly to site content

NIOSHTIC-2 Publications Search

Search Results

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

Authors
Evans-CD; LaDow-K; Schumann-BL; Savage-RE Jr.; Caruso-J; Vonderheide-A; Succop-P; Talaska-G
Source
Carcinogenesis 2004 Apr; 25(4):493-497
NIOSHTIC No.
20025659
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: five mice, -BaP/-arsenic; five 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 nmol BaP/25 ml acetone (or acetone alone) was applied topically, once per day for 4 days. DNA was extracted from skin and lung and assayed by (32)P-postlabeling. 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 PAH interactions in lung carcinogenesis.
Keywords
Arsenic-compounds; Laboratory-animals; Animals; Animal-studies; Polycyclic-aromatic-hydrocarbons; Exposure-levels; Carcinogenesis; Carcinogens; Carcinogenicity; Epidemiology; Occupational-exposure; Workers; Work-environment; Lung-cancer; Smoking; Pulmonary-system-disorders; Respiratory-system-disorders; In-vivo-studies; In-vitro-studies
Contact
University of Cincinnati, Department of Environmental Health, 3223 Eden Avenue, Cincinnati, OH 45267-0056, USA
CODEN
CRNGDP
CAS No.
7440-38-2; 7440-23-5; 50-32-8
Publication Date
20040401
Document Type
Journal Article
Email Address
talaskgg@ucmail.uc.edu
Funding Amount
1070124
Funding Type
Grant
Fiscal Year
2004
NTIS Accession No.
NTIS Price
Identifying No.
Grant-Number-T42-CCT-510420
Issue of Publication
4
ISSN
0143-3334
NIOSH Division
DART
Priority Area
Research Tools and Approaches: Control Technology and Personal Protective Equipment
Source Name
Carcinogenesis
State
OH
Performing Organization
Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio
TOP