Faculty Collaboration Database

Effect of early vs. late administration of 4-hydroxyphenylretinamide (4-HPR) on N-methyl-N-nitrosourea (MNU)-induced mammary tumorigenesis. J Cell Biochem Suppl 1997;27:92-9

Date

01/01/1997

Pubmed ID

9591198

DOI

10.1002/(sici)1097-4644(1997)27+<92::aid-jcb15>3.0.co;2-n

Scopus ID

2-s2.0-0031325821 (requires institutional sign-in at Scopus site)   4 Citations

Abstract

Mammary tumors were induced in 48-52-day-old female Sprague-Dawley rats in metestrus or diestrus with a single jugular injection of MNU (50 mg/kg). Control rats received the saline vehicle (Group 4 n = 9). Rats were fed 4% Teklad diet containing either 0 (Group 3, n = 20) or 782 mg 4-HPR/kg diet. 4-HPR supplementation was initiated either 1 week prior to (Group 1, n = 14) or 4 weeks following MNU administration (Group 2, n = 19). Neither body weight nor food intake differed significantly between treatment groups. Feeding of 4-HPR 1 week prior to tumor induction reduced the number of tumors (0.8 +/- .2) when compared to MNU control rats (2.1 +/- .4). Immunohistochemical staining of mammary tumor sections for PCNA was quantitated by microdensitometry and expressed as an HSCORE. No differences in HSCORE were observed between tumor groups although the percentage of nuclear area occupied by intermediate and darkly stained nuclei was reduced in the late 4-HPR group. GC-->AT transitions in codon 12 of the H-ras gene were detected in 50% (12/24) of MNU control tumors, 60% (6/10) of early 4-HPR tumors, and 38% (6/16) of late 4-HPR tumors. Mutation rates did not differ significantly between groups. 4-HPR appears to be a more effective chemopreventive when fed during the initiation period.

Author List

Crist KA, Wang Y, Lubet RA, Steele VE, Kelloff GJ, You M

MESH terms used to index this publication - Major topics in bold

Animals
Anticarcinogenic Agents
Base Sequence
Carcinogens
Codon
DNA Primers
Drug Administration Schedule
Feeding Behavior
Female
Fenretinide
Genes, ras
Immunohistochemistry
Mammary Neoplasms, Experimental
Methylnitrosourea
Mutation
Rats
Rats, Sprague-Dawley
S Phase
Weight Gain