Diallyl sulfide induces the expression of estrogen metabolizing genes in the presence and/or absence of diethylstilbestrol in the breast of female ACI rats.
Diethylstilbestrol (DES) induces mammary tumors in female ACI rats and is associated with an increased risk of developing breast cancer in humans. Diallyl sulfide (DAS) has been shown to prevent cancer in animals. Previously, we have shown that DAS inhibits the production of DES induced DNA adducts when given prior to DES. We hypothesize that DAS alters the expression of genes responsible for DES metabolism. To test this hypothesis, four groups of 10 female ACI rats were treated daily for four days as follows: (1) corn oil, (2) 50mg/kg DES, (3) 50mg/kg DAS, and (4) 50mg/kg DAS+50mg/kg DES. RNA was isolated from breast tissue and mRNA levels of CYP1A1, CYP1B1, glutathione-S-transferase (GST) and superoxide dismutase (SOD) were analyzed by real-time PCR. DES, DAS, and DES/DAS treatments increased the expression of CYP1A1 by 2.1-, 4.7-, and 12.7-fold, respectively. Similar results were seen for CYP1B1. DES decreased the expression of GST by 23%, whereas DAS and DAS/DES treatments increased the expression of GST by 12- and 16.7-fold, respectively. Similar results were seen with SOD. These results suggests that DAS may prevent the formation of DES induced DNA damage by altering the expression of DES metabolizing genes.
Green
Mario
M
College of Pharmacy, Florida A&M University, 302 West Pershing St, Tallahassee, FL 32307, United States. mgreen06@hotmail.com
Newell
Oneil
O
Aboyade-Cole
Ayoola
A
Darling-Reed
Selina
S
Thomas
Ronald D
RD
D000498:Allyl Compounds / Q000494:pharmacology*; D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D001189:Aryl Hydrocarbon Hydroxylases / Q000235:genetics; D001940:Breast / Q000187:drug effects* / Q000201:enzymology; D002273:Carcinogens / Q000494:pharmacology; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics; D065633:Cytochrome P-450 CYP1B1; D018736:DNA Adducts; D004054:Diethylstilbestrol / Q000494:pharmacology*; D004967:Estrogens / Q000378:metabolism; D004968:Estrogens, Non-Steroidal / Q000494:pharmacology; D005260:Female; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D005982:Glutathione Transferase / Q000235:genetics; D015227:Lipid Peroxidation; D051381:Rats; D011912:Rats, Inbred ACI; D013440:Sulfides / Q000494:pharmacology*; D013482:Superoxide Dismutase / Q000235:genetics
D000498:Allyl Compounds; D016588:Anticarcinogenic Agents; D002273:Carcinogens; D018736:DNA Adducts; D004967:Estrogens; D004968:Estrogens, Non-Steroidal; D013440:Sulfides; C038491:allyl sulfide; D004054:Diethylstilbestrol; D001189:Aryl Hydrocarbon Hydroxylases; C585496:CYP1B1 protein, human; C585499:Cyp1b1 protein, rat; D019363:Cytochrome P-450 CYP1A1; D065633:Cytochrome P-450 CYP1B1; D013482:Superoxide Dismutase; D005982:Glutathione Transferase