Mechanisms Underlying the Increased Susceptibility of the Immature Mammary Gland to Selected Carcinogens
Abstract
The immature human breast is more susceptible than the mature breast to the carcinogenic effects of ionizing radiation. Studies have demonstrated that immature rat mammary epithelial cells (RMECs) are more susceptible than their mature counterparts to the cytolethal effects of ionizing radiation and N-nitroso-N-methylurea (NMU) but not dimethylbenzanthracene (DMBA). The work reported here was undertaken to further explore this age-differential carcinogen-specific mammary epithelial cell susceptibility. The goal is to determine whether immature RMECs are also more susceptible than mature RMECs to the mutagenic effects of NMU, possibly due to differences in the repair of NMU- induced DNA damage. Using the Big Blue(c) transgenic mutagenesis assay system, it was discovered that more mutants persist in immature than mature RMECs following NMU treatment in vivo. Comet assays revealed that while there were no age-related differences immediately following NMU treatment in vitro, immature but not mature RMECs display increased tail moments beginning two hours following NMU treatment. Apoptosis does not cause the difference. Mature RMECs mimicked the immature RMEC response after benzylguanine pretreatment, which inhibits methylguanine methyltransferase (MGMT); such treatment did not affect immature RMECs. The data support the working hypothesis that immature RMECs are deficient in MGMT activity relative to mature RMECs.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2001
- Accession Number
- ADA396469
Entities
People
- Jennifer L. Ariazi
- Michael Gould
Organizations
- University of Wisconsin–Madison