The utility of multiple-section sampling in the histopathological evaluation of the kidney for carcinogenicity studies.
In a recent review of 379 carcinogenicity studies in rodents conducted under the auspices of the National Cancer Institute and, later, the National Toxicology Program (NTP), the kidneys were the third most frequent site for chemical-related neoplasia. While some potent carcinogens induced high incidences of renal neoplasms with shortened latency in Fischer-344 (F-344) rats or B6C3F1 mice, other usually nonmutagenic compounds produced marginally increased incidences of renal neoplasms that were difficult to interpret. As an aid to the interpretation of 16 recent studies, additional kidney sections from rats or mice were prepared and examined microscopically. The remaining pieces of formalin-fixed kidney were embedded and sectioned at intervals of 1 mm (rats) or 0.5 mm (mice) to produce an additional 6-8 (rats) or 4-6 (mice) H&E-stained sections per kidney per animal for microscopic examination. The average number of additional sections per animal was similar between dosed and control groups to avoid sampling bias. The supplemental evaluation of these additional kidney sections was clearly useful in determining potential renal carcinogenicity in male F-344 rats in these NTP studies. Of the 13 studies in male rats in which step-sections of kidney were evaluated, the supplemental data demonstrated conclusively an association between chemical administration and renal tubule hyperplasia, adenoma, or both in 9 studies. For 3 chemicals, the evidence of an association with renal proliferative lesions in male rats remained uncertain. In contrast, the supplemental evaluation of step-sections was less useful for female rats, male mice, and female mice, largely because such evaluations generally revealed few if any additional neoplasms. For these sex-species groups, there were only two instances, both involving male mice, in which the additional data confirmed an association with kidney neoplasia.
Eustis
S L
SL
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709.
Hailey
J R
JR
Boorman
G A
GA
Haseman
J K
JK
D000236:Adenoma / Q000139:chemically induced / Q000473:pathology; D000818:Animals; D015197:Carcinogenicity Tests / Q000379:methods*; D002277:Carcinoma / Q000139:chemically induced / Q000473:pathology; D005260:Female; D006652:Histological Techniques; D006965:Hyperplasia / Q000139:chemically induced / Q000473:pathology; D007680:Kidney Neoplasms / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D051381:Rats; D011916:Rats, Inbred F344