The environmental
estrogen, dichlorodiphenyltrichloroethane (
DDT), and its metabolites have been implicated in the development of
breast cancer through mechanisms that remain to be elucidated. It has been hypothesized that exposure to
DDT and its metabolites, during critical periods of development, can contribute to an elevated risk for
breast cancer in adults. In the present study, we have investigated the effect of
o,p'-DDT on mammary gland cell proliferation and chromosomal alterations, in a rat
mammary cancer model (commonly used to study human
cancer), to gain insights into its potential role in the development of
breast cancer. Twenty-one-day-old female Sprague-Dawley (SD) rats were administered
o,p'-DDT, 7,12-dimethylbenz[a]
anthracene (DMBA),
genistein, DDT+DMBA, or
DDT+DMBA+
genistein, over a 14-day period. To determine changes in chromosome number and structure, we used the micronucleus assay as well as multicolor fluorescence in situ hybridization (FISH) region-specific
DNA probes for rat chromosomes 4 and 19. Cell proliferation was evaluated using
5-bromo-2'-deoxyuridine (
BrdU). Significant increases in
BrdU-incorporated cells were seen in the rats treated with DDT+DMBA. Although micronucleus frequencies were somewhat elevated in several of the treatment groups, significant increases were not seen in any of them. Significant increases in numerical
chromosomal aberrations were detected in all of the
DDT- and DMBA-treated groups.
Genistein significantly reduced
BrdU incorporation and
polyploidy in the DDT+DMBA-treated rats. These initial studies indicate that
DDT and DMBA can induce cellular and chromosomal alterations in the rat mammary gland, which is consistent with the hypothesis that these agents can induce early events in mammary
carcinogenesis.