Comparison of Past and Recent Historical Control Data in Relation to Spontaneous Tumors During Carcinogenicity Testing in Fischer 344 Rats

Abstract

Abstract:In the present survey, the historical data for spontaneous tumors observed in our laboratory was compared in relation to the time-related changes between recent (2000)(2001)(2002)(2003)(2004) and past (1990-1999) samples from Fischer 344 rats used in carcinogenicity studies. In the recent samples, there were statistically increased incidences of islet cell adenomas in males and uterine adenocarcinomas in females. On the other hand, there were decreased incidences of pheochromocytomas, prostatic adenomas, pituitary anterior adenomas, large granular lymphocytic (LGL) leukemias and Leydig cell tumors in males and pituitary anterior adenomas in females. Furthermore, there were decreases in the body weights of both sexes at 58 weeks of age in the recent samples, and this may have been related to the decreases in the incidences of pheochromocytomas, Leydig cell tumors, prostatic adenomas and LGL leukemias. Moreover, the decreased incidence of pheochromocytoma in males revealed a positive correlation with a decreased percentage of severe chronic progressive nephropathy (CPN). On the other hand, there were no distinct factors responsible for increased incidences of tumors observed in the recent samples, suggesting a possible genetic drift. In conclusion, the incidences of spontaneous tumors obtained in our laboratory have been changed with time. Smaller body weights in both sexes and reduction in the number of male cases with severe CPN might be related to the reduced incidence of certain types of tumors in recent animals. (J Toxicol Pathol 2008; 21: 53-60)

Transition of Historical Control Data for High Incidence Tumors in F344 Rats

“…The incidence of uterine adenocarcinoma was 3.3% in 1990–1999, 12.0% in 2000–2004 and 13.5% in 2005–2009. Thus the incidences of pancreatic islet cell adenoma in males and uterine adenocarcinoma tended to increase from around 2000 as stated in the previous report 3 .…”

“…The two left columns are our previous data 3 and the right column is the present data. The incidences of C-cell adenoma in the thyroid were 17.4% and 20.1% for males and 11.5% and 11.8% for females in 1990–1999 and 2000–2004, respectively, and 30.8% for males and 24.4% for females in 2005–2009, and the incidence tended to increase in both sexes in recent years.…”

“…Gotemba Laboratory, BoZo Research Center Inc. (Gotemba, Shizuoka, Japan), has used Fischer 344 rats for carcinogenicity studies since the 1990s, as well as other major strains including Sprague-Dawley (SD) and Wistar rats. The historical control data for common tumors in F344 rats in our facility were reported previously 3 . In the present report, we update the data from the last 5 years and compare them with previous data to examine the transition of tumor incidences over the years.…”

Review of results published by Mesnage et al. (2015) in PLoS ONE and the laboratory findings communicated by Dr Samsel to Farm Wars

“…Prejean et al, 1973;Durbin et al, 1966). The difference in the incidence of such lesions between strains, their contributing factors and their trends have been studied extensively and are well documented in the literature (e.g., Carlus et al, 2013;Kuroiwa et al, 2013;Ando et al, 2008;Baldrick, 2005;Brix et al, 2005;Tennekes et al, 2004;Keenan et al, 2002;Eiben and Bomhard, 1999;Haseman et al, 1998). The overall consensus is that different genetic predispositions underlie the development of these lesions for each strain.…”

“…Carlus et al, 2013;Kuroiwa et al, 2013;Ando et al, 2008;Baldrick, 2005;Brix et al, 2005;Tennekes et al, 2004;Keenan et al, 2002;Eiben and Bomhard, 1999;Haseman et al, 1998). In general, such genetic drift is more common with outbred Wistar and Sprague-Dawley rats.…”