1999, Rásonyi, Thomas, Schlatter, Josef, Dietrich, Daniel R.

The mycotoxin ochratoxin A (OTA) was shown to be a potent kidney carcinogen in rats demonstrating a marked sex difference in the response. Compared to female rats, male rats had a 10-fold higher incidence of kidney carcinomas. The objective of this study was to investigate whether this sex difference in tumor response is due to an exacerbation of effect resulting from the interaction of the male rat specific urinary protein α2u-globulin (α2u) with OTA. Male and female rats were treated by oral gavage with OTA (1 mg/kg per day), D-limonene (dL; 1650 mg/kg per day) as a positive control or corn oil for 7 consecutive days. OTA induced severe renal lesions predominantly in the P3 region of the proximal tubules. The lesions consisted of necrotic cells and cell exfoliations. No hyaline droplets were found in the P2 segment following OTA treatment, whereas dL induced the expected accumulation of droplets. The results suggest that OTA induced kidney lesions are in all characteristic points different from the known α2u-nephropathy induced by dL. Based on these experiments the male rat specific protein α2u does not seem to be involved in the mechanism(s) leading to the high tumor incidence observed in OTA exposed male rats.

1994, Dietrich, Daniel R., Candrian, Regula, Marsman, Daniel S., Popp, James A., Kaufmann, William K., Swenberg, James A.

Cell proliferation (S phase response) in archival liver tissues of partially hepatectomized rats was determined via proliferating cell nuclear antigen (PCNA) immunohistochemistry. These results were compared with the S phase response assessed previously in the same tissues via tritiated thymidine (Tdr) autoradiography. The effect of prolonged tissue fixation on PCNA immunohistochemistry was compared in two studies: study A, the liver was fixed for a maximum of 7 days and then embedded in paraffin and stored for not, vert, similar 18 months, while in study B, the liver was fixed in formalin for 7 years and then embedded in paraffin and stored for not, vert, similar 18 months until sectioning and immunostaining. PCNA immunostaining was successful in the liver sections of both studies, irrespective of the length of formalin fixation. Furthermore, the S phase labeling indices (LI) determined via PCNA and Tdr were comparable, although not identical, in the two studies. Therefore, use of PCNA immunohistochemistry should allow retrospective staining of rodent tissues for the assessment of cell proliferative activity in formalin-fixed organs from previously conducted toxicity and carcinogenicity studies.