A single-dose protocol for azaserine initiation of pancreatic carcinogenesis in the rat

✍ Scribed by James D. Yager Jr.; Bill D. Roebuck; Joanne Zurlo; Daniel S. Longnecker; Edward O. Weselcouch; Seri A. Wilpone

• Publisher: John Wiley and Sons
• Year: 1981
• Tongue: French
• Weight: 585 KB
• Volume: 28
• Category: Article
• ISSN: 0020-7136
• DOI: 10.1002/ijc.2910280511

✦ Synopsis

Abstract

Previously, the induction of pancreatic carcinogenesis in the rat using azaserine has involved a multiple‐dose treatment protocol. The objective of the present study was to determine the effect of multiple azaserine treatments on pancreatic DNA synthesis and to develop a protocol for a single‐dose initiation of pancreatic carcinogenesis by azaserine in the rat. Pancreatic DNA synthesis in young rats, which was determined by measuring the amount of [^3^H]‐thymidine incorporation into DNA, was found to be elevated at 4.3 weeks of age and to decrease to a baseline level by 6.3 weeks. Treatment of 4‐week‐old rats with azaserine resulted in a dose‐dependent inhibition of [^3^H]‐thymidine incorporation into both pancreatic and liver DNA. Maximum inhibition was seen at 10 mg/kg body weight. This inhibition was followed by a gradual return of incorporation to normal values over a 48 h period. One week following pretreatment with four weekly injections of azaserine at 30 mg/kg, [^3^H]‐thymidine incorporation into pancreatic and liver DNA was significantly elevated, suggesting that multiple injection protocols cause enhanced DNA synthesis which could have a co‐carcinogenic and/or promotional effect. Single‐doses of azaserine (10, 30 and 60 mg/kg) given at 7 weeks of age caused the appearance of more atypical acinar cell nodules (AACN) than when given at 5 weeks of age. The most effective dose was 30 mg/kg. Using alkaline elution, we determined that this response was due to the occurrence of more DNA damage in the 7‐week‐old animals. Thus, these results demonstrate a rationale for the use of single‐dose initiation protocols in the pancreas. An effective single‐dose protocol for induction of AACN in azaserine‐treated rats fed semi‐synthetic diet is presented.