The formation of DNA adducts is considered to be a mechanism by which structurally diverse chemicals produce mutations and cancer. The P-32- Postlabeling method is sensitive technique that can be used to detect lipophilic or bulky adducts in preparations of DNA. Using this technique, we previously demonstrated multiple DNA adducts in preparations of human lymphocyte DNA. In another study, the P-32-postlabeling method was used to evaluate the formation and persistence of DNA adducts in the mammary glands of parous and non-parous mice treated with benzo[a]pyrene. One major adduct was detected on thin-layer maps of DNA digests of treated animals. This same adduct, which co-migrated with a 7,8,9,10-tetra hydrobenzo[a]pyrene (BPDE-dG) standard, was also the major adduct in digests of DNA obtained from mouse mammary gland mince exposed in vitro to benzo[a]pyrene. These findings demonstrate that the mammary gland has the capacity to metabolize this procarcinogen to DNA-reactive electrophiles. DNA adduct formation was not apparently restricted to the glandular component since the gland-free (""""""""cleared"""""""" fat pad) tissue also formed the major DNA adduct in vivo. The persistence of the major adduct was evident by the fact that DNA digest of glands of intact animals obtained four weeks after treatment still revealed this adduct. So far, we have not observed any differences in parous vs. non-parous mice with regard to pattern or persistence of adducts.

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Intramural Research (Z01)
Project #
1Z01ES070069-09
Application #
3855969
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
1991
Total Cost
Indirect Cost
City
State
Country
United States
Zip Code