Hexachlorobenzene promoted breast cancer and increased insulin receptor content in NMU-treated rats

RANDI A; COCCA C; NUÑEZ M; CROCI M; GUTIERREZ A; BERGOC R; KLEIMAN DE PISAREV D

Lisbon

Congreso; 12th International Congress of Endocrinology; 2004

Background of Study: Hexachlorobenzene (HCB) is an organochlorine environmental contaminant which elicits thyroid and reproductive dysfunctions. Controversy still exists about the breast carcinogenic properties of this compound. Objectives: Our aim was to study the effect of HCB on: (i) the promotion of N-nitroso-N-methylurea (NMU)-induced mammary tumours, (ii) Insulin Receptor (IR) levels and (iii) microsomal and cytosolic Protein Tyrosine Kinase (PTK) activities in mammary glands and tumours. Methods: Female Sprague Dawley rats were injected with NMU (50 mg/kg b.w.) at 50, 80 and 110 days old. HCB (10 mg/100 g b.w.) was administered from 65 to 110 days of age. The following groups were studied: Control, NMU, HCB and NMU-HCB. Results: Tumour incidence, number/rat and volume were higher in NMU-HCB than in NMU rats (p<0.05, p<0.05 and p<0.0001 respectively). The latency period was not altered by HCB. A higher cellular indifferentiation and number of positive PCNA (Cyclin/proliferating cell nuclear antigen) cells were observed in NMU-HCB versus NMU. HCB increased the immunodetectable IR levels in HCB (p<0.01) and in NMU (p<0.05) groups compared to their respective controls . Immunoblotting with antiphosphotyrosine antibodies also revealed a higher content in HCB (p<0.02) and NMU (p<0.001) rats vs. control. HCB decreased microsomal PTK activity in mammary glands (p<0.001) and tumours (p<0.001), without alterations in the cytosolic PTK activity. Conclusions: The data presented in this study demonstrated for the first time that HCB is a tumour promoter of mammary NMU-induced carcinogenesis and suggest that alterations in IRs levels and protein tyrosyl phosphorylation could be involved in the mechanism of action of the pesticide.