PMID- 16596229
OWN - NLM
STAT- MEDLINE
DCOM- 20060524
LR  - 20061115
IS  - 1019-6439 (Print)
IS  - 1019-6439 (Linking)
VI  - 28
IP  - 5
DP  - 2006 May
TI  - The aspirin metabolite, salicylate, inhibits 7,12-dimethylbenz[a]anthracene-DNA 
      adduct formation in breast cancer cells.
PG  - 1131-40
AB  - There is evidence that aspirin and other non-steroidal anti-inflammatory drugs 
      may be protective agents against cancer in the gastrointestinal tract. These 
      effects are particularly well documented for the colon and rectum. Some 
      epidemiological and experimental studies have suggested that aspirin could also 
      be a chemopreventive agent against breast cancer. We investigated the effects of 
      the aspirin metabolite, salicylate (SA), on 7,12-dimethylbenz[a]anthracene 
      (DMBA)-DNA adduct formation as well as on the expression of the enzymes involved 
      in the carcinogen bioactivation pathway, in particular cytochrome P450 1A (CYP1A) 
      and cyclooxygenases (COX-1 and COX-2). The effects of the test drug were examined 
      in both the human mammary carcinoma cell line, MCF-7, and mammary cells derived 
      from DMBA-induced rat mammary tumours (RMTCs). In this study, we also reported 
      the effects of SA on cell growth and viability in breast cancer cells (BCCs). The 
      results demonstrated that DMBA-DNA adduct formation in both cancer cell lines was 
      inhibited by SA at concentrations of > or = 2.5 mM. CYP1A was undetectable in 
      RMTCs while CYP1A induction by beta-naphthoflavone in MCF-7 cells was 
      significantly inhibited by SA in a concentration-dependent manner. Aspirin did 
      not affect COX-1 expression in either of the BCCs. COX-2 was not detected in 
      MCF-7 cells, but its expression in RMTCs was inhibited by SA treatment, which 
      also significantly reduced BCC growth, but failed to cause cell death by necrosis 
      or apoptosis. These data suggest that inhibition of DMBA-DNA adduct formation may 
      contribute to aspirin breast cancer chemopreventive action and indicate that this 
      drug can act in the first stage of carcinogenesis.
FAU - Abbadessa, Giuliana
AU  - Abbadessa G
AD  - Dipartimento di Scienze Cliniche e Biologiche, Universita di Torino, Torino, 
      Italy.
FAU - Spaccamiglio, Angela
AU  - Spaccamiglio A
FAU - Sartori, Maria Luisa
AU  - Sartori ML
FAU - Nebbia, Carlo
AU  - Nebbia C
FAU - Dacasto, Mauro
AU  - Dacasto M
FAU - Di Carlo, Francesco
AU  - Di Carlo F
FAU - Racca, Silvia
AU  - Racca S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Int J Oncol
JT  - International journal of oncology
JID - 9306042
RN  - 0 (7,12-dimethylbenz(a)anthracene-DNA adduct)
RN  - 0 (Cyclooxygenase 2 Inhibitors)
RN  - 0 (Cyclooxygenase Inhibitors)
RN  - 0 (DNA Adducts)
RN  - 0 (Salicylates)
RN  - 57-97-6 (9,10-Dimethyl-1,2-benzanthracene)
RN  - EC 1.14.14.1 (Cytochrome P-450 CYP1A1)
RN  - EC 1.14.99.1 (Cyclooxygenase 1)
RN  - EC 1.14.99.1 (Cyclooxygenase 2)
SB  - IM
MH  - 9,10-Dimethyl-1,2-benzanthracene/*analogs & derivatives/antagonists & 
      inhibitors/toxicity
MH  - Animals
MH  - Breast Neoplasms/pathology
MH  - Cell Line, Tumor
MH  - Cyclooxygenase 1/genetics
MH  - Cyclooxygenase 2/genetics
MH  - Cyclooxygenase 2 Inhibitors/pharmacology
MH  - Cyclooxygenase Inhibitors/pharmacology
MH  - Cytochrome P-450 CYP1A1/genetics
MH  - DNA Adducts/*antagonists & inhibitors
MH  - Female
MH  - Humans
MH  - Mammary Neoplasms, Experimental/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Salicylates/*pharmacology
EDAT- 2006/04/06 09:00
MHDA- 2006/05/25 09:00
CRDT- 2006/04/06 09:00
PHST- 2006/04/06 09:00 [pubmed]
PHST- 2006/05/25 09:00 [medline]
PHST- 2006/04/06 09:00 [entrez]
PST - ppublish
SO  - Int J Oncol. 2006 May;28(5):1131-40.