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And Michelson, A. M. (1969). Polynucleotide analogues. XIV. poly rc -dimethylguanylate. Biochim. Biophys. Acta 182, 17. 1. Interactions between PAH's and Cellular Macromolecules 35 94. , Weinstein, I. B. , and Grunberger, D. (1977). Conformation of DNA modified with a dihydrodiol epoxide derivative of benzo[αJpyrene. Biochemistry 16, 3127. 95. Rogan, E. , and Cavalier, E. (1976). Metabolic activation of aromatic hydrocarbons in purified rat liver nuclei. Proc. Natl. Acad. Sei. A. 73, 457. 96.

This high d e g r e e of substitution w a s r e q u i r e d t o o b s e r v e an easily detectable c h a n g e in t h e structure a n d function of D N A . With the m e t h o d s e m p l o y e d , w e could only e x a m i n e effects o n the total D N A s a m p l e rather than o n t h e structure and function of single g e n e s ; it is difficult, therefore, t o e x t r a p o l a t e from t h e p r e s e n t results t o t h e in vivo situation. If, h o w e v e r , qualitatively similar b u t quantitatively less e x t e n s i v e c h a n g e s o c c u r in vivo w h e n cells are e x p o s e d to B P , then the c a r c i n o g e n could p r o d u c e aberrations in t h e transcription of genetic information.

T h e starting point is certainly an interaction b e t w e e n the c h e m i c a l or s o m e d e r i v e d metabolites and i m p o r t a n t m o l e c u l e s of t h e cell, such as proteins a n d D N A . A part of t h e p r o b l e m can b e d i s c u s s e d at the m o l e c u l a r scale. B u t c a n c e r is a d i s e a s e of a c o m p l i c a t e d a n i m a l , as a m a m m a l . T h e r e f o r e , to u n d e r s t a n d t h e w h o l e p r o c e s s , w e m u s t shift our focus from the m o l e c u l a r level to the a n i m a l level.

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