This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Stewart, B. W. Articles by Farber, E. Search for Related Content PubMed PubMed Citation Articles by Stewart, B. W. Articles by Farber, E.

Alterations in Thermal Stability of Rat Liver Chromatin and DNA Induced in Vivo by Dimethylnitrosamine and Diethylnitrosamine¹

Fels Research Institute and Departments of Pathology and Biochemistry, Temple University School of Medicine, Philadelphia, Pennsylvania 19140

A study was made of the effects of administration to rats of dimethylnitrosamine and diethylnitrosamine on the transition temperature (T_m) of sheared chromatin and DNA isolated from the liver. The analysis was made by thermal chromatography on hydroxylapatite with the use of DNA prelabeled with [³H]thymidine and following the elution pattern during the operation of a continuous temperature gradient. With a nonnecrogenic dose of dimethylnitrosamine (10 mg/kg), the alterations in chromatin were maximal at 24 hr and disappeared by 3 days. Greatest differences in elution profiles of chromatin after dimethylnitrosamine treatment were observed in the region above 80°. Administration of the carcinogen caused a lowering of the "melting" curve in this region, the displacement from control position being proportional to the dose. The maximum dose (60 mg/kg) displaced the complete chromatin melting curve up to 5° to the lower side. DNA isolated from this chromatin melted 3° less than that from control rats. However, administration of lower doses of dimethylnitrosamine did not affect the melting profile of DNA. The administration of diethylnitrosamine caused a similar type of change. However, the modification was also seen at 50–60°.

¹ This investigation was supported in part by USPHS Research Grants CA-12218, CA-12227 (from the National Cancer Institute), and AM-14482 (from the National Institute of Arthritis, Metabolism and Digestive Diseases) and by grants from the American Cancer Society (BC-7N and PRP-39) and the National Health and Medical Research Council of Australia.

² Present address: School of Pathology, University of New South Wales, P.O. Box 1, Kensington, N.S.W. 2033 Australia, where part of this investigation was conducted.

³ Present address: Department of Pathology, University of Toronto, 100 College Street, Toronto, Canada M5G 1L5. To whom requests for reprints should addressed.

Received 7/28/77. Accepted 11/23/77.