Yonsei Med J.  1969 Dec;10(2):117-124. 10.3349/ymj.1969.10.2.117.

The Effects of Methontrexate on the Pancreas of Rats: A Histochemical and Ultrastructural Study

• Choi HY
• Kim CS
• Lee YB

• KMID: 1107452
• DOI: http://doi.org/10.3349/ymj.1969.10.2.117

Abstract

Methonexate is one of the well known anti-cancer chemotherapeutic agents and exerts its action by inhibiting mitoses by inhibition of nucleic acid synthesis. Its effect on actively proliferating normal and pathologic tissues have been well documented. However, little information is available on its effect on tissue which shows no active mitoses but does have a very active metabolic process, such as the pancreas. The present study investigated the histochemical and ultrastructural changes which take place within 24 hours after a single intraperitoneal injection of methotrexate. Using a light microscope for observation, no .specific or constant alteration was noted except for a mild acinar cell dissociation 18 hours after the injection. However, electron microscopic observations showed that several organelles of pancreatic acinar cell revealed ultrastructural changes such as vesiculation and dilation of the cisternae of endoplasmic reticulum, and the appearance of autophagic vacuoles which contained cellular organelles, and showed hyperplasia and dilation of Golgi complexes. The nuclei and zymogen granules were not significantly altered. The changes of endoplasmic reticulum were ,distinctly seen from 1 hour after the injection and were most severe at 6 hours. Autophagic vacuoles appeared at 6 hours and had progressively increased in number and size 18 hours after the injection. Similar changes were also reported in experimental animals which were treated with several cytotoxic agents. According to this study, it is evident that a single administration of methotrexate within short time interval induced a series of ultrastructural alterations in several organelles of the pancreatic acinar cells. It is not clear as yet whether or not this is a specific reaction of cells to methotrexate.

MeSH Terms

Animals
Female
Male
Methotrexate/*pharmacology
Pancreas/cytology/*drug effects
Rats