Chemoprevention of chemically-induced mammary carcinogenesis by indole-3-carbinol.
Indole-3-carbinol, a component of cruciferous vegetables, was evaluated for it efficacy in the prevention of chemically-induced mammary tumors using three different protocols. Because this compound was unstable, it was administered by gavage rather than in the diet. A preliminary dose range study revealed that dose levels of 100 and 50 mg/day, 5x/week, were not toxic to female Sprague-Dawley rats. Initial studies in the DMBA model showed that administering indole-3-carbinol during the initiation and promotion phases were highly effective chemopreventive methods (91-96% reduction in cancer multiplicity). Subsequent studies showed that the administration of indole-3-carbinol only during the initiation phase (7 days prior to until 7 days post DMBA) was also highly effective as a chemopreventive agent. Determination of enzyme levels in the livers of animals treated long-term with indole-3-carbinol showed high levels of induction of various phase I and phase II drug metabolizing enzymes. Finally, indole-3-carbinol when administered both prior to and after MNU (a direct acting carcinogen) caused a significant decrease (65%) in mammary tumor multiplicity. These results support previous studies that indole-3-carbinol can prevent mammary carcinogenesis by direct and indirect acting carcinogens. Therefore, indole-3-carbinol might be a good candidate for chemoprevention of breast cancer in women.
Grubbs
C J
CJ
Department of Nutrition Sciences, University of Alabama at Birmingham 35924, USA.
Steele
V E
VE
Casebolt
T
T
Juliana
M M
MM
Eto
I
I
Whitaker
L M
LM
Dragnev
K H
KH
Kelloff
G J
GJ
Lubet
R L
RL
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D016588:Anticarcinogenic Agents / Q000627:therapeutic use*; D019362:Cytochrome P-450 CYP2B1; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D005982:Glutathione Transferase / Q000096:biosynthesis; D007211:Indoles / Q000627:therapeutic use*; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D008770:Methylnitrosourea; D010088:Oxidoreductases / Q000096:biosynthesis / Q000378:metabolism; D051381:Rats; D011916:Rats, Inbred F344; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D013379:Substrate Specificity; D013997:Time Factors
D016588:Anticarcinogenic Agents; D007211:Indoles; D015127:9,10-Dimethyl-1,2-benzanthracene; D008770:Methylnitrosourea; D003577:Cytochrome P-450 Enzyme System; C016517:indole-3-carbinol; D010088:Oxidoreductases; D019362:Cytochrome P-450 CYP2B1; D005982:Glutathione Transferase