Viscometric analysis of DNA damage in kidney and lung following exposure of rats to small doses of chemical carcinogens

Abstract

A new viscometric technique has been used lo detect DNA damage in kidney and lung of rats treated with six chemical carcinogens. In alkaline conditions (pH 12.5) the reduced viscosity (η _red ) of kidney and lung DNA from control rats increased slowly with time reaching a maximum, (η _red ) ^max , after 9–12 h. Carcinogens, by inducing DNA strand breaks either chemically or indirectly by excision repair or during incubation in alkali, cause a reduction of DNA supercoiling which can be sensitively measured by monitoring changes in viscosity. Computerized analysis of time-viscosity curves showed that a statistically significant reduction of the time required for (η _red ) to reach 95% of its maximum value ( t-95 ) was induced by the following single i.p. doses: N-nitrosodimethylamine (DMN), kidney 0.07 mg/kg, lung 0.28 mg/kg; N-nitrosodiethylamine (DEN), kidney 3.2 mg/kg, lung 12.8 mg/kg; N-nitroso-N-methylurea, kidney and lung 0.5 mg/kg; 1,2-dimethyIhydrazine (DMH), kidney 1 mg/kg, lung 16 mg/kg; 4-nitroquinoline-l-oxide (NQO), kidney 2.5 mg/kg, lung 0.63 mg/kg; 2-acetylamino-fluorene, kidney and lung 12.5 mg/kg. The decrease of t-95 was constantly dose-related. The comparison with data previously obtained from liver demonstrates that DMN, DEN, DMH and NQO caused the greatest amount of DNA damage in the organ most susceptible to tumor induction. Viscosity changes elicited by DMN, DEN and DMH are quantitatively wdl correlated with the extent of DNA alkyla-tion.