Long term tumorigenicity of a single application of indomethacin or Amuno in adolescent and in adult male Sprague Dawley rats.
200 adolescent (Group I) and 200 adult male Sprague Dawley rats (Group II) were divided into 4 subgroups of 50 animals each. Animals were treated on the 29th (Group I) or 98th day of life (Group II) either with acetone or Amuno carrier in acetone or Amuno on acetone (2.5 mg indomethacin/100 g animal weight in acetone) or with the pure substance indomethacin 2.5 mg/100 g of animal weight in acetone, giving a single application on the shaved dorsal skin. Subsequently the animals remained under observation until their deaths, followed by autopsy and histopathologic examination of several organs. The rats treated with Amuno of indomethacin in the adolescent stage showed lower body weights and a shorter total survival time. The adolescent animals treated with Amuno or indomethacin showed a significantly higher rate of interstitial testicular tumors of the Leydig tumor type, adenomas and adenocarcinomas of the small and large intestine as well as hepatocellular tumors. The total number of neoplasias was higher in the animals treated with Amuno or indomethacin compared to those treated with acetone or carrier with acetone. Application of Amuno or indomethacin also resulted in a higher rate of hyperplasias (sole of foot, lymph nodes, prostate). The impairment of the synthesis of prostaglandins caused by indomethacin apparently results in starting complex pathomechanisms which have effects until the late death of the animals. Adolescent animals were affected more frequently by the application of indomethacin as were already adult animals.
Goerttler
K
K
German Cancer Research Center Heidelberg, Institute of Experimental Pathology.
Edler
L
L
Loehrke
H
H
D000375:Aging; D000818:Animals; D001835:Body Weight; D004817:Epidermis / Q000473:pathology; D006965:Hyperplasia / Q000139:chemically induced; D007213:Indomethacin / Q000633:toxicity*; D007984:Leydig Cell Tumor / Q000139:chemically induced; D008114:Liver Neoplasms, Experimental / Q000139:chemically induced; D008297:Male; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced; D009374:Neoplasms, Experimental / Q000139:chemically induced* / Q000401:mortality; D051381:Rats; D017207:Rats, Sprague-Dawley; D012878:Skin Neoplasms / Q000139:chemically induced; D013736:Testicular Neoplasms / Q000139:chemically induced
D007213:Indomethacin