Related Experiment Videos
Wide-range linear dose-response curve for DNA binding of orally administered benzo(a)pyrene in mice
Abstract:
The binding of p.o. benzo(a)pyrene (BP) to the DNA of mice was investigated. With a single dose of 1 microgram, levels of DNA binding were highest in the liver, followed by the intestine, colon, and stomach. In all organs, the majority of DNA-associated radioactivity was in the form of adducts which did not release ethyl acetate-soluble BP tetrols on acid hydrolysis. In both stomach and liver, the formation of acid-hydrolyzable and non-acid-hydrolyzable BP-DNA adducts was linearly related to dose, over a carcinogen dosage range of 10(-8) to 10(-3) g (liver) or 10(-7) to 10(-3) g (stomach). Repair or removal via cell turnover of liver BP-DNA adducts over a period of 7 days proceeded with the same efficiency when the dose of the administered carcinogen was varied over a range of 100,000-fold. These results suggest that in vivo the initial interaction between DNA and ingested BP takes place in the same manner both at high doses typical of laboratory carcinogenesis experiments and at low doses typical of human exposure.
Insights
Oral benzo(a)pyrene (BP) binds to mouse DNA, primarily forming non-hydrolyzable adducts in organs like the liver and stomach. Adduct formation and removal rates are dose-independent, suggesting consistent DNA interaction across exposure levels.
Area of Science:
- Toxicology
- Molecular Biology
- Carcinogenesis
Background:
- Benzo(a)pyrene (BP) is a common environmental carcinogen found in tobacco smoke and grilled foods.
- Understanding BP's interaction with DNA is crucial for assessing cancer risk.
- Previous studies have shown BP can form DNA adducts, but dose-response and repair mechanisms require further investigation.
Purpose of the Study:
- To investigate the in vivo binding of orally administered benzo(a)pyrene (BP) to mouse DNA.
- To characterize the types of BP-DNA adducts formed and their distribution in various organs.
- To determine the dose-dependency and repair kinetics of BP-DNA adducts in the liver.
Main Methods:
- Mice were administered varying doses of benzo(a)pyrene (BP) orally.
- DNA was isolated from different organs (liver, intestine, colon, stomach) at various time points.
- Radioactivity associated with DNA was quantified to measure BP-DNA binding.
- Acid hydrolysis was used to differentiate between hydrolyzable and non-hydrolyzable BP-DNA adducts.
Main Results:
- DNA binding of BP was highest in the liver, followed by the intestine, colon, and stomach after a single dose.
- The majority of BP-DNA adducts were non-acid-hydrolyzable in all organs studied.
- Both acid-hydrolyzable and non-acid-hydrolyzable adduct formation in the liver and stomach showed a linear relationship with BP dose.
- Repair or removal of liver BP-DNA adducts occurred with consistent efficiency across a 100,000-fold range of BP doses.
Conclusions:
- The initial interaction between ingested BP and DNA in vivo is consistent across a wide range of doses, from low environmental exposures to high experimental levels.
- Non-hydrolyzable BP-DNA adducts are the predominant form, indicating stable DNA modifications.
- The dose-independent efficiency of adduct repair suggests cellular mechanisms can handle BP-induced DNA damage effectively regardless of exposure magnitude.