Extrapolating carcinogenesis data from animals to humans.

Abstract

Extrapolation of bioassay data from high to low doses and from laboratory animal to the human is essential for future growth of the chemical industries and the safeguard of human health and th environment. To be effective this process requires a solid data base: Metabolism of the chemicals holds many clues regarding their carcinogenic hazards, and studies in liver, kidney, and the specific target organs and their cellular organelles are needed. Other environmental chemicals may alter the effects of a single pollutant by enzyme induction or inhibition in liver or target organ (in cytosol, endoplasmic reticulum, or nuclear membranes) and may cause shunts to alternate pathways which must be explored at different dose levels. DNA repair needs further exploration with attention to the molecular location of attachment of the electrophile to DNA bases and the ability of the target cell for effective repair. Inhibition of DNA repair by environmental chemicals needs better understanding. The synergistic effects of chemicals contribute to the complexity of proper extrapolation of data. Cocardinogenicity is not a laboratory curiosity but a real-life situation. Specific human genetic defects involving DNA repair or immunologic competence may further complicate the issues and need exploration.