Faculty Collaboration Database

Evaluation of dose and treatment duration on the esophageal tumorigenicity of N-nitrosomethylbenzylamine in rats. Carcinogenesis 1995 Feb;16(2):259-65

Date

02/01/1995

Pubmed ID

7859357

DOI

10.1093/carcin/16.2.259

Scopus ID

2-s2.0-0028870067 (requires institutional sign-in at Scopus site)   46 Citations

Abstract

N-Nitrosomethylbenzylamine (NMBA) is a potent esophagus-specific carcinogen that has been utilized extensively in the study of esophageal carcinogenesis in rats. While many studies have focused on the pathogenesis of NMBA-induced esophageal tumors, the tumorigenicity of NMBA itself has not been thoroughly investigated in any single, systematic dose-response study. Therefore, in this study we evaluated NMBA tumorigenicity in rats following various short-term s.c. treatment regimens with the aim of developing an abbreviated treatment protocol which could be used in future studies. To assess the possible correlation of basal cell proliferation with NMBA tumorigenicity, we evaluated the expression of proliferating cell nuclear antigen (PCNA) in both control and NMBA-treated rats. In rats which received a cumulative NMBA dosage of 7.5 mg/kg over the course of 5 weeks, tumor incidence and multiplicity were as follows: 40% with 0.4 +/- 0.3 tumors/rat at week 10; 100% with 2.2 +/- 1.0 tumors/rat at week 20; and 100% with 2.3 +/- 1.0 tumors/rat at week 30. These rats exhibited marked increases in basal cell labeling, with indices that were 1.5- to 1.8-fold higher than controls. NMBA treatment regimens of shorter duration with equivalent or higher cumulative dosages were generally ineffective in producing esophageal tumors, even though significantly elevated levels of basal cell proliferation occurred. Together, these findings indicate that the duration of NMBA treatment is of critical importance in the tumorigenic potential of the carcinogen.

Author List

Siglin JC, Khare L, Stoner GD

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

Animals
Body Weight
Carcinogens
Cell Division
Dimethylnitrosamine
Dose-Response Relationship, Drug
Drug Administration Schedule
Eating
Esophageal Neoplasms
Esophagus
Evaluation Studies as Topic
Injections, Subcutaneous
Male
Proliferating Cell Nuclear Antigen
Rats
Rats, Inbred F344