The role of alpha 2u-globulin in ochratoxin A induced renal toxicity and tumors in F344 rats

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 differenc e in tumor response is due to an exacerbation of effect resulting from the interaction of the male rat specific urinary protein alpha 2u-globulin (alp ha 2u) 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 contro l or corn oil for 7 consecutive days. OTA induced severe renal lesions pred ominantly in the P-3 region of the proximal tubules. The lesions consisted of necrotic cells and cell exfoliations. No hyaline droplets were found in the P-2 segment following OTA treatment, whereas dL induced the expected ac cumulation of droplets. The results suggest that OTA induced kidney lesions are in all characteristic points different from the known alpha 2u-nephrop athy induced by dL. Based on these experiments the male pat specific protei n alpha 2u does not seem to be involved in the mechanism(s) leading to the high tumor incidence observed in OTA exposed male rats. (C) 1999 Elsevier S cience Ireland Ltd. All rights reserved.