Mechanisms Underlying the Increased Susceptibility of the Immature Mammary Gland to Selected Carcinogens
Abstract
Despite intense epidemiological studies of mature women ionizing radiation is the only agent commonly accepted to cause breast cancer. The immature breast is more susceptible than the mature breast to the carcinogenic effects of ionizing radiation; perhaps the same is true of chemicals. This project's goal is to determine whether immature rat mammary epithelial cells (RMECs) are more susceptible to the mutagenic effects of N-nitroso-N-methylurea (NMU) and begin to explore reasons for that susceptibility. Work reported last year revealed that immature RMECs are indeed more susceptible than mature RMECs to the mutagenic effects of NMU; results hinted that immature RMECs were deficient in methylguanine methyltransferase (MGMT) activity relative to mature RMECs. This year, an assay was developed to measure MGMT activity. RMEC MGMT activity is much lower than MGMT activity in liver, which displays no age-related difference. In contrast, immature RMECs have 2/5 less MGMT activity than mature RMECs (p = 0.0127). This DNA repair deficiency in immature RMECs could contribute to age-differential mutagenesis. These results warrant further studies of age-related DNA repair differences and suggest that epidemiological studies of adult women should focus on progression while efforts to identify initiating agents would be better directed at immature girls.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jun 01, 2002
- Accession Number
- ADA407224
Entities
People
- Jennifer L. Ariazi
- Michael Gould
Organizations
- University of Wisconsin–Madison