Oncological Outcomes in Rats Given Nephrocarcinogenic Exposure to Dietary Ochratoxin A, Followed by the Tumour Promoter Sodium Barbital for Life: A Pilot Study

Toxins

Peter G. Mantle¹  Miloslav Dobrota³  Cheryl E. Gillett²  Edward W. Odell⁴ 

[1] Centre for Environmental Policy, Imperial College London, London, UKHedley Atkins Breast Pathology Laboratory, Guy’s Hospital, London, UK;Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, UK;Department of Oral Pathology, King’s College London, London, UK;

关键词: DNA ploidy;    latency;    mononuclear leukaemia;    renal tumour;    mammary tumour;    angiosarcoma;   

DOI  :  10.3390/toxins2040552

来源: mdpi

【 摘 要 】

The potent experimental renal carcinogenesis of ochratoxin A (OTA) in male rats makes the dietary contaminant a potential factor in human oncology. We explored whether the tumour promoter sodium barbitate could shorten the otherwise long latency between exposure to toxin and tumourigenesis. Young rats, of a hybrid in which mononuclear leukaemia was rare, were given feed contaminated (5 ppm) with OTA for 36 weeks to initiate renal tumourigenesis. Some individuals were thereafter given sodium barbitate (500 ppm in drinking water) for life. Pathological outcomes were studied at or near the end of natural life. Renal tumours in males given barbitate became evident after latency of one year, but only slightly before those without barbitate. In contrast, female mammary tumourigenesis was advanced by at least 6 months synchronously in all rats given the OTA-barbitate regimen compared to tumourigenesis in controls. Diagnosis of malignant mammary angiosarcoma in a female given the OTA-barbitate regimen is a new finding in the rat. The long latency of OTA-induced renal tumourigenesis was not notably susceptible to accelerated promotion by barbitate, contrasting with an apparently marked effect of barbitate on development of mammary tumours.

【 授权许可】

CC BY   
© 2010 by the authors; licensee Molecular Diversity Preservation International, Basel, Switzerland