Effects of adsorption of benzo [a] pyrene onto carbon black particles on levels of DNA adducts in lungs of rats exposed by inhalation
RK Wolff, JA Bond, JD Sun, RF Henderson… - Toxicology and applied …, 1989 - Elsevier
RK Wolff, JA Bond, JD Sun, RF Henderson, JR Harkema, WC Griffith, JL Mauderly…
Toxicology and applied pharmacology, 1989•ElsevierExposure of rodents to benzo [a] pyrene (BaP) associated with particles has previously been
shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA
damage might be enhanced, DNA adducts were measured in lungs of F344 rats following
inhalation of pure BaP aerosols or BaP absorbed on carbon black particles. Groups of rats
were exposed nose only to filtered air,[14C] BaP (2 mg/m3), or [14C] BaP (2 mg/m3)
adsorbed on carbon black (97 mg/m3)(BaP CB) for 4 hr/day, 1 day/week, for 12 weeks …
shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA
damage might be enhanced, DNA adducts were measured in lungs of F344 rats following
inhalation of pure BaP aerosols or BaP absorbed on carbon black particles. Groups of rats
were exposed nose only to filtered air,[14C] BaP (2 mg/m3), or [14C] BaP (2 mg/m3)
adsorbed on carbon black (97 mg/m3)(BaP CB) for 4 hr/day, 1 day/week, for 12 weeks …
Exposure of rodents to benzo[a]pyrene (BaP) associated with particles has previously been shown to result in increased retention of BaP and metabolites in lungs. To determine if DNA damage might be enhanced, DNA adducts were measured in lungs of F344 rats following inhalation of pure BaP aerosols or BaP absorbed on carbon black particles. Groups of rats were exposed nose only to filtered air, [14C]BaP (2 mg/m3), or [14C]BaP (2 mg/m3) adsorbed on carbon black (97 mg/m3) (BaP CB ) for 4 hr/day, 1 day/week, for 12 weeks. Groups of rats were terminated at 4, 8, 12, 16, 20, and 24 weeks after the beginning of the 12-week exposure period. Retention of total 14C in lungs was used as an indicator of total reactive metabolites. DNA isolated from lungs was analyzed for adducts using a 32P-postlabeling assay. Inhalation of BaP CB resulted in 100-fold higher levels of 14C in lungs at the end of the 12-week exposure than did inhalation of pure BaP. The halftime for the decline in 14C levels was 34 ± 3 weeks (mean ± SE) for rats exposed to BaP CB and 6 ± 2 weeks for rats exposed to pure BaP. At the end of 12 weeks of exposure, DNA adducts in lungs of rats exposed to pure BaP ranged from 2–15 adducts per 109 bases (mean = 7, n = 4) and in rats exposed to BaP adsorbed on carbon black ranged from 10–12 adducts per 109 bases (mean = 11, n = 4); DNA adducts in lungs of sham-exposed rats ranged from 0–2 adducts per 109 bases (mean = 1, n = 4). The halftimes for the decline in DNA adducts in lungs were 3 ± 1 weeks (mean ± SE) for the rats exposed to BaP CB and 5 ± 2 weeks for the rats exposed to BaP. One of the DNA adducts found following exposure to both BaP and BaP CB was tentatively identified as the BaP diol epoxide deoxyguanosine (BPDE) adduct. Levels of both total and BPDE DNA adducts were significantly increased (p < 0.05) in lungs of rats exposed to both BaP and BaP CB compared to levels in lungs of sham-exposed rats. There were no significant differences in levels of DNA adducts in lungs of rats exposed to BaP or BaP CB , although the pattern of adducts was different between the two exposure modes. These data point to the importance of determining specific damage to DNA in the form of adducts as an indicator of potential genotoxic effects as opposed to relying on levels of total 14C.
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