Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression

Michael J Wargovich, Arnaldo Jimenez, Kathy McKee, Vernon E. Steele, Marco Velasco, Johnnie Woods, Roger Price, Kenneth Gray, Gary J. Kelloff

Research output: Contribution to journalArticle

227 Citations (Scopus)

Abstract

We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal antiinflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1149-1155
Number of pages7
JournalCarcinogenesis
Volume21
Issue number6
StatePublished - 2000
Externally publishedYes

Fingerprint

Aberrant Crypt Foci
Azoxymethane
Colon
Piroxicam
ferulic acid
Inbred F344 Rats
Carcinogens
Meclizine
Carcinogenesis
Glucaric Acid
Phenylbutyrates
Farnesol
Chlorpheniramine
Ketoprofen
Rutin
Injections
Diclofenac
Methylene Blue
Histamine Antagonists
Taurine

ASJC Scopus subject areas

  • Cancer Research

Cite this

Wargovich, M. J., Jimenez, A., McKee, K., Steele, V. E., Velasco, M., Woods, J., ... Kelloff, G. J. (2000). Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis, 21(6), 1149-1155.

Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. / Wargovich, Michael J; Jimenez, Arnaldo; McKee, Kathy; Steele, Vernon E.; Velasco, Marco; Woods, Johnnie; Price, Roger; Gray, Kenneth; Kelloff, Gary J.

In: Carcinogenesis, Vol. 21, No. 6, 2000, p. 1149-1155.

Research output: Contribution to journalArticle

Wargovich, MJ, Jimenez, A, McKee, K, Steele, VE, Velasco, M, Woods, J, Price, R, Gray, K & Kelloff, GJ 2000, 'Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression', Carcinogenesis, vol. 21, no. 6, pp. 1149-1155.
Wargovich MJ, Jimenez A, McKee K, Steele VE, Velasco M, Woods J et al. Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. Carcinogenesis. 2000;21(6):1149-1155.
Wargovich, Michael J ; Jimenez, Arnaldo ; McKee, Kathy ; Steele, Vernon E. ; Velasco, Marco ; Woods, Johnnie ; Price, Roger ; Gray, Kenneth ; Kelloff, Gary J. / Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression. In: Carcinogenesis. 2000 ; Vol. 21, No. 6. pp. 1149-1155.
@article{efb3d88698ea48fcbb490aab11d314ef,
title = "Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression",
abstract = "We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal antiinflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.",
author = "Wargovich, {Michael J} and Arnaldo Jimenez and Kathy McKee and Steele, {Vernon E.} and Marco Velasco and Johnnie Woods and Roger Price and Kenneth Gray and Kelloff, {Gary J.}",
year = "2000",
language = "English (US)",
volume = "21",
pages = "1149--1155",
journal = "Carcinogenesis",
issn = "0143-3334",
publisher = "Oxford University Press",
number = "6",

}

TY - JOUR

T1 - Efficacy of potential chemopreventive agents on rat colon aberrant crypt formation and progression

AU - Wargovich, Michael J

AU - Jimenez, Arnaldo

AU - McKee, Kathy

AU - Steele, Vernon E.

AU - Velasco, Marco

AU - Woods, Johnnie

AU - Price, Roger

AU - Gray, Kenneth

AU - Kelloff, Gary J.

PY - 2000

Y1 - 2000

N2 - We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal antiinflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.

AB - We assessed the effects of 78 potential chemopreventive agents in the F344 rat using two assays in which the inhibition of carcinogen-induced aberrant crypt foci (ACF) in the colon was the measure of efficacy. In both assays ACF were induced by the carcinogen azoxymethane (AOM) in F344 rats by two sequential weekly injections at a dose of 15 mg/kg. Two weeks after the last AOM injection, animals were evaluated for the number of aberrant crypts detected in methylene blue stained whole mounts of rat colon. In the initiation phase protocol agents were given during the period of AOM administration, whereas in the post-initiation assay the chemopreventive agent was introduced during the last 4 weeks of an 8 week assay, a time when ACF had progressed to multiple crypt clusters. The agents were derived from a priority listing based on reports of chemopreventive activity in the literature and/or efficacy data from in vitro models of carcinogenesis. During the initiation phase carboxyl amidoimidazole, p-chlorphenylacetate, chlorpheniramine maleate, D609, diclofenac, etoperidone, eicosatetraynoic acid, farnesol, ferulic acid, lycopene, meclizine, methionine, phenylhexylisothiocyanate, phenylbutyrate, piroxicam, 9-cis-retinoic acid, S-allylcysteine, taurine, tetracycline and verapamil were strong inhibitors of ACF. During the post-initiation phase aspirin, calcium glucarate, ketoprofen, piroxicam, 9-cis-retinoic acid, retinol and rutin inhibited the outgrowth of ACF into multiple crypt clusters. Based on these data, certain phytochemicals, antihistamines, non-steroidal antiinflammatory drugs and retinoids show unique preclinical promise for chemoprevention of colon cancer, with the latter two drug classes particularly effective in the post-initiation phase of carcinogenesis.

UR - http://www.scopus.com/inward/record.url?scp=0034131115&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034131115&partnerID=8YFLogxK

M3 - Article

C2 - 10837003

AN - SCOPUS:0034131115

VL - 21

SP - 1149

EP - 1155

JO - Carcinogenesis

JF - Carcinogenesis

SN - 0143-3334

IS - 6

ER -