Reinhold J. Laib

Covalent binding of drug metabolites to DNA — a tool of predictive value?

The presently available data suggest at least some correlation between covalent binding of drug metabolites to DNA and carcinogenicity of that drug. More data, however, are needed to establish the predictability of covalent DNA binding assays for extrahepatic cancer. A covalent binding assay requires administration of radioactively labelled compound to the experimental animals; the availability of labelled compound and requirements as to radiochemical purity, chemical and biochemical stability are limiting the applicability of this procedure. Many technical pitfalls accompany covalent DNA binding assays. It is concluded that at the present time DNA binding assays do not represent routine procedures within a standard test battery for carcinogenicity, but are invaluable for more in-depth research which probably follows routine testing.

Metabolic Activation and Pharmacokinetics in Hazard Assessment of Halogenated Ethylenes

Halogenated ethylenes play an important role in occupational and environmental medicine. Several attempts at toxicological evaluation of such compounds have been recently published (Maltoni 1977; Lee et al. 1978; Gehring et al. 1979; Kappus and Ottenwalder 1980; Henschler et al. 1980; Bolt 1980). The principal question is that of possible carcinogenicity. It is now clear that vinyl chloride (Maltoni 1977) and vinyl bromide (Bolt et al. 1979) are carcinogenic; some data also argue in favor of carcinogenicity of vinylidene chloride (Lee et al. 1978). Trichloroethylene (Henschler et al. 1980) and perchloroethylene (Bolt and Link 1980), according to present data, appear devoid of cancerogenic potency. These differences in biological behavior of such closely related compounds can only be explained on a biochemical basis (Bonse and Henschler 1976).