Morphologic Changes and Ha - ras Mutation in DMBA - treated Rat Mammary Tissues

Kim, Yong Hoon; Cho, Hyun Deuk; Kim, Kwang II; Lee, Joo Han; Lee, Hyun Ho; Kim, Young Sik; Kim, Han Kyeom; Kim, In Sun

Abstract

PURPOSE: To understand the morphologic and molecular changes in carcinogen-induced breast tissues, DMBA (10-dimethy1-1,2 benzanthracene) was administrated in Sprague- Dawley female rats.
MATERIALS AND METHODS
At 50 days of age, all experimental rats were given 20 mg DMBA by gastric intubation. Until the seventh week after DMBA administration, six rats were sacrificed every week, thereafter all tumors found during 20 weeks were removed every week. The morphologic changes were evaluated in routinely processed sections stained with H-E and with anti-smooth muscle actin antibody. Mutation of Ha-ras codons 12 and 61 was examined by ARMS (amplification refractory mutation system) method in frozen tissues.
RESULTS
The epithelial cell proliferation of terminal end buds began 2 weeks after DMBA treatment and progressed to the 6th week, resulting in microscopic malignant tumor in one of the 7th weeks rats. The tumors were developed in 43 of 62 rats (69.4%); 8 benign lesions in 4 rats and 72 malignant tumors in 39 rats. Mutations in the 12th and 61th codon of Ha-ras gene were respectively found in 29.7% and 2.7% of preneoplastic breasts, 25% in benign lesions, 2.6% and 31.6% of malignant tumors.
CONCLUSION
DMBA treatment in rats induced epithelial proliferation, then benign and malignant tumors through Ha-ras gene mutation, especially in codon 61 leading to cancer.