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Effect of early vs. late administration of 4‐Hydroxyphenylretinamide (4‐HPR) on N‐Methyl‐N‐Nitrosourea (MNU)‐induced mammary tumorigenesis
Author(s) -
Crist Keith A.,
Wang Yian,
Lubet Ronald A.,
Steele Ver E.,
Kelloff Gary J.,
You Ming
Publication year - 1997
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/(sici)1097-4644(1997)27+<92::aid-jcb15>3.0.co;2-n
Subject(s) - mammary tumor , medicine , endocrinology , carcinogenesis , immunohistochemistry , saline , proliferating cell nuclear antigen , carcinogen , chemistry , cancer , breast cancer , biochemistry
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. J. Cell. Biochem. Suppl. 27:92–99. © 1998 Wiley‐Liss, Inc.