Mechanisms of chemical carcinogenesis: recent advances.

The carcinogenetic risk assessment of veterinary drugs has to be envisaged as part of food toxicology. The authors review the recent discoveries which have proved significant for the toxicologist. Tumours arise from an inherited transformation of normal cells through genotoxic, perigenetic and epigenetic processes. Genotoxic mechanisms are best understood and have led to the development of short-term reference tests. The biochemistry of DNA alterations is being unravelled and permits quantitative estimation of carcinogenetic potencies. Work on the role of oncogenes is providing new clues to the understanding the mechanisms of chemical carcinogenesis. Perigenetic processes deal mainly with DNA repair systems and emphasize the complexity of human genome dynamics. Experimental findings about epigenetic mechanisms are still inconclusive as to their practical implications. Abnormal expression of HLA-antigens at the surface of neoplastic cells has been reported, but its significance is still unknown. In conclusion, the main source of progress in toxicology undoubtedly comes from molecular biology, but experimental results must be interpreted with caution if practical issues are to be derived from them.