Secondary effects induced by the colon carcinogen azoxymethane in BDIX rats

Azoxymethane (AOM) is claimed to be a colon-specific carcinogen. In our studies, AOM was administered to adult BDIX/OrlIco rats by four weekly subcutaneous injections of 15 mg/kg body weight each - two periods of 2 weeks of AOM treatment separated by a one-week break. This treatment schedule resulted in colon carcinomas with a high frequency (75-100%) and with a high reproducibility. However, some serious side effects are associated with this carcinogen treatment. In addition to the colorectal tumours, we found small intestinal tumours, hepatic lesions and a high frequency of mesenchymal renal tumours which increased with longer latency periods. The renal tumours were only found in female rats, and this indicates a possible relation to sex hormones. We therefore analyzed both male and female kidneys for the expression of estrogen and progesterone receptors by immunohistochemical methods. A positive nuclear reaction for estrogen receptor was present in most tumour cells in all tumours and occasionally in nuclei of entrapped tubular cells, but never in glomeruli. Normal appearing renal tissue from female rats showed no positive reaction, but in male rats a slight nuclear reaction was seen in tubuli in the peripheral part of the medulla. A similar pattern was seen for progesterone receptors, but less pronounced. No rats developed tumours in the external ear canal, which is in contrast to studies performed in other rat strains. This may therefore be strain related. In order to reduce the secondary effects of the induction of colon cancer by AOM, it is advisable to use male rats only and a maximum latency period of 32 weeks.