PMID- 11927004
OWN - NLM
STAT- MEDLINE
DCOM- 20020620
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 1876-4673 (Electronic)
IS  - 0910-5050 (Linking)
VI  - 93
IP  - 3
DP  - 2002 Mar
TI  - Induction of apoptosis by sulindac in azoxymethane-induced possible colonic 
      premalignant lesions in rats.
PG  - 242-6
AB  - We have reported that beta-catenin-accumulated crypts (BCAC), which do not have 
      the appearance of aberrant crypt foci (ACF) are possible colonic premalignant 
      lesions in rats. Suppression of the occurrence and advancement of such lesions 
      should have critical relevance to cancer prevention. This study examined whether 
      sulindac, a chemopreventive nonsteroidal anti-inflammatory drug is able to induce 
      apoptosis in such premalignant lesions. At 6 weeks of age, rats groups 1 - 3 were 
      given azoxymethane (AOM) (15 mg/kg-body weight) once weekly for 3 weeks. Two 
      groups were given sulindac in the diet (200 and 400 ppm), starting at 9 weeks of 
      age. The rats were sacrificed at the termination, and the colons were carefully 
      examined. The incidence and crypt multiplicity of BCAC and ACF were significantly 
      less than those of the control group. The effect of sulindac on the expression of 
      BCAC was greater than that on ACF. Exposure to sulindac significantly increased 
      the apoptotic index (terminal deoxynucleotide transferase dUTP nick-end labeling 
      (TUNEL)-positive cells) in BCAC. However, no significant increase of the index 
      was found in the case of ACF. These results suggest that the chemopreventive 
      effect of sulindac in rats is related to the induction of apoptosis in 
      premalignant lesions. Our results also provide additional evidence that BCAC are 
      premalignant lesions in colon carcinogenesis in rodents.
FAU - Kuno, Toshiya
AU  - Kuno T
AD  - First Department of Pathology, Gifu University School of Medicine, Gifu 500-8705, 
      Japan.
FAU - Yamada, Yasuhiro
AU  - Yamada Y
FAU - Hirose, Yoshinobu
AU  - Hirose Y
FAU - Katayama, Masaki
AU  - Katayama M
FAU - Sakata, Keiko
AU  - Sakata K
FAU - Hara, Akira
AU  - Hara A
FAU - Saji, Shigetoyo
AU  - Saji S
FAU - Mori, Hideki
AU  - Mori H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (Anti-Inflammatory Agents, Non-Steroidal)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Carcinogens)
RN  - 0 (Ctnnb1 protein, rat)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - 184SNS8VUH (Sulindac)
RN  - 3M4G523W1G (Silver)
RN  - MO0N1J0SEN (Azoxymethane)
SB  - IM
MH  - Animals
MH  - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/*drug effects
MH  - Azoxymethane/toxicity
MH  - Carcinogens/toxicity
MH  - Cell Division
MH  - Cell Nucleus/metabolism
MH  - Colonic Neoplasms/metabolism/pathology/*prevention & control
MH  - Cytoskeletal Proteins
MH  - Diet
MH  - In Situ Nick-End Labeling
MH  - Incidence
MH  - Male
MH  - Nucleolus Organizer Region/metabolism
MH  - Precancerous Conditions/metabolism/pathology/*prevention & control
MH  - Rats
MH  - Rats, Inbred F344
MH  - Silver/chemistry
MH  - Sulindac/*pharmacology
MH  - *Trans-Activators
MH  - beta Catenin
PMC - PMC5926969
EDAT- 2002/04/03 10:00
MHDA- 2002/06/21 10:01
PMCR- 2002/03/01
CRDT- 2002/04/03 10:00
PHST- 2002/04/03 10:00 [pubmed]
PHST- 2002/06/21 10:01 [medline]
PHST- 2002/04/03 10:00 [entrez]
PHST- 2002/03/01 00:00 [pmc-release]
AID - CAE242 [pii]
AID - 10.1111/j.1349-7006.2002.tb02164.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 2002 Mar;93(3):242-6. doi: 10.1111/j.1349-7006.2002.tb02164.x.