PMID- 15880734
OWN - NLM
STAT- MEDLINE
DCOM- 20050930
LR  - 20131121
IS  - 0893-6692 (Print)
IS  - 0893-6692 (Linking)
VI  - 46
IP  - 1
DP  - 2005 Jul
TI  - Induction of cell proliferation, micronuclei and hyperdiploidy/polyploidy in the 
      mammary cells of DDT- and DMBA-treated pubertal rats.
PG  - 43-52
AB  - 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.
CI  - (c) 2005 Wiley-Liss, Inc.
FAU - Uppala, Padma T
AU  - Uppala PT
AD  - Department of Environmental & Occupational Health, School of Public Health, Loma 
      Linda University, Loma Linda, CA 92350, USA. puppala@sph.llu.edu
FAU - Roy, Shambhu K
AU  - Roy SK
FAU - Tousson, Albert
AU  - Tousson A
FAU - Barnes, Stephen
AU  - Barnes S
FAU - Uppala, Gurunatha R
AU  - Uppala GR
FAU - Eastmond, David A
AU  - Eastmond DA
LA  - eng
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (Carcinogens)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - CIW5S16655 (DDT)
RN  - DH2M523P0H (Genistein)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/toxicity
MH  - Animals
MH  - Carcinogens/*toxicity
MH  - Cell Proliferation/*drug effects
MH  - DDT/toxicity
MH  - Drug Synergism
MH  - Female
MH  - Genistein/toxicity
MH  - In Situ Hybridization, Fluorescence
MH  - Mammary Glands, Animal/cytology/*drug effects/growth & development
MH  - Micronuclei, Chromosome-Defective/*chemically induced
MH  - Micronucleus Tests
MH  - *Polyploidy
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2005/05/10 09:00
MHDA- 2005/10/01 09:00
CRDT- 2005/05/10 09:00
PHST- 2005/05/10 09:00 [pubmed]
PHST- 2005/10/01 09:00 [medline]
PHST- 2005/05/10 09:00 [entrez]
AID - 10.1002/em.20131 [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 2005 Jul;46(1):43-52. doi: 10.1002/em.20131.