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Selective Alteration of Rapidly-Labeled Ribonucleic Acid Synthesis in Rat Liver during Azo-Dye Carcinogenesis¹

( Chester Beatty Research Institute, Institute of Cancer Research, Royal Cancer Hospital, Fulham Road, London, England)

Patterns of mRNA³ synthesis in rat liver during carcinogenesis due to FDAB have been analyzed by countercurrent distribution. The changes induced by this dye were different in type and extent from those following the administration of the noncarcinogenic analog, AB. Early changes in mRNA pattern due to FDAB were reversible, later changes were irreversible, while those due to AB remained reversible for several months. mRNA patterns in livers containing primary hepatomas showed great variability. These findings suggest that the early effects of FDAB are due to reversible alterations in DNA transcription, while subsequent effects involve alteration of the DNA or permanent changes in transcription.

¹ This investigation has been supported by grants to the Chester Beatty Research Institute (Institute of Cancer Research: Royal Cancer Hospital) from the Medical Research Council and the British Empire Cancer Campaign for Research, and by the Public Health Service research grant CA-03188-08 from the National Cancer Institute, USPHS.

³ The abbreviations used are: DNA, deoxyribonucleic acid; RNA, ribonucleic acid; mRNA, messenger RNA, i.e. rapidlylabeled RNA sedimenting > 4S, prepared by the 4-aminosalicylate method; AB, aminoazobenzene; FDAB, 4'-fluoro-4-dimethyl-aminoazobenzene.

² Arthur A. Thomas Cancer Research Fellow of the Anti-Cancer Council of Victoria; present address: The Baker Medical Research Institute, Melbourne, Australia.

Received 7/22/64. Revised 11/ 9/64.

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