PMID- 10814878
OWN - NLM
STAT- MEDLINE
DCOM- 20000718
LR  - 20211203
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 155
IP  - 1
DP  - 2000 Jul 3
TI  - Inhibition of benzo[a]pyrene- and 1,6-dinitropyrene-DNA adduct formation in human 
      mammary epithelial cells bydibenzoylmethane and sulforaphane.
PG  - 47-54
AB  - Numerous phytochemicals have been examined for their capacity to act as cancer 
      chemopreventive agents. Dibenzoylmethane, a minor constituent of licorice and a 
      compound structurally-related to curcumin, recently was identified as an 
      effective inhibitor of chemically-induced rat mammary DNA-adduct formation and 
      tumorigenesis (Carcinogenesis 19(1998)1039-1043). The present studies were 
      conducted to examine the capacity of dibenzoylmethane to inhibit the formation of 
      DNA adducts following exposure to benzo[a]pyrene (BP) and 1,6-dinitropyrene 
      (1,6-DNP), and to stimulate the expression of glutathione-S-transferase (GST) and 
      NAD(P)H-quinone reductase (QR) proteins in the human mammary epithelial cell line 
      MCF-10F. In addition, the efficacy of dibenzoylmethane as an enzyme inducer and 
      adduct inhibitor was compared with that of sulforaphane, a potent inducer of 
      phase II detoxification enzymes and inhibitor of chemically-induced rat mammary 
      tumorigenesis. Dibenzoylmethane at concentrations from 0.1 M to 2.0 microM 
      inhibited BP-DNA adduct formation by 63 to 81%. Likewise, sulforaphane inhibited 
      BP-DNA adduct formation by 68 to 80% over the same concentration range. DNA 
      adduct formation following exposure to 1,6-DNP was significantly inhibited by 46 
      to 61% due to dibenzoylmethane treatment (0.1 to 2.0 microM) and 30 to 56% due to 
      sulforaphane treatment at the same concentrations. The expression of QR and 
      GSTP1-1 proteins were increased by 3 to 4-fold and 3 to 5-fold, respectively, for 
      MCF-10F cells treated with sulforaphane (0.5-2.0 microM). Dibenzoylmethane 
      treatment at the same concentrations did not induce GSTP1-1 expression and 
      significantly stimulated QR expression only at the 2.0 microM concentration. 
      These data indicate that human mammary epithelial MCF-10F cells can convert BP 
      and 1,6-DNP to DNA-binding forms, and that DNA adduct formation can be inhibited 
      by the phytochemicals dibenzoylmethane and sulforaphane. The inhibition of BP-DNA 
      and 1, 6-DNP adduct formation by sulforaphane was associated with increases in QR 
      and GST protein expression. The mechanisms underlying the capacity of 
      dibenzoylmethane to inhibit BP-DNA and 1,6-DNP-DNA adduct formation could not be 
      explained by changes in QR or GST expression and remain to be determined. 
      Together these data suggest that dibenzoylmethane and sulforaphane warrant 
      continued evaluation as breast cancer chemopreventive agents.
FAU - Singletary, K
AU  - Singletary K
AD  - Department of Food Science and Human Nutrition, University of Illinois, 905 South 
      Goodwin Avenue, Urbana 61801, USA. kws@uiuc.edu
FAU - MacDonald, C
AU  - MacDonald C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Anticarcinogenic Agents)
RN  - 0 (Benzoates)
RN  - 0 (Chalcones)
RN  - 0 (Isothiocyanates)
RN  - 0 (Pyrenes)
RN  - 0 (Sulfoxides)
RN  - 0 (Thiocyanates)
RN  - 3417WMA06D (Benzo(a)pyrene)
RN  - 66Q2ZUF83N (1,6-dinitropyrene)
RN  - ANS7ME8OKC (dibenzoylmethane)
RN  - EC 1.6.- (NADH, NADPH Oxidoreductases)
RN  - EC 2.5.1.18 (Glutathione Transferase)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Anticarcinogenic Agents/pharmacology
MH  - Benzo(a)pyrene/*antagonists & inhibitors/metabolism
MH  - Benzoates/*pharmacology
MH  - Breast/*metabolism
MH  - Cell Line
MH  - *Chalcones
MH  - Dose-Response Relationship, Drug
MH  - Electron Transport Complex I
MH  - Epithelium/*metabolism
MH  - Glutathione Transferase/metabolism
MH  - Humans
MH  - Immunoblotting
MH  - Isothiocyanates
MH  - NADH, NADPH Oxidoreductases/metabolism
MH  - Protein Binding
MH  - Pyrenes/*metabolism
MH  - Sulfoxides
MH  - Thiocyanates/*pharmacology
EDAT- 2000/05/18 09:00
MHDA- 2000/07/25 11:00
CRDT- 2000/05/18 09:00
PHST- 2000/05/18 09:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/05/18 09:00 [entrez]
AID - S0304-3835(00)00412-2 [pii]
AID - 10.1016/s0304-3835(00)00412-2 [doi]
PST - ppublish
SO  - Cancer Lett. 2000 Jul 3;155(1):47-54. doi: 10.1016/s0304-3835(00)00412-2.