Arylamines mutations

Although 1-aminopyrene is a reduced metabolite of 1-nitropyrene, this arylamine will not covalently bind to DNA in vitro (72). In contrast, when incubations were conducted with the intermediate reduction product, N-hydroxy-l-aminopyrene, extensive covalent binding to DNA was detected (72). This observation is consistent with the previous report that several N-hydroxy arylamines formed DNA adducts and induced mutations in S. typhimurium (116), and suggests that, at least for 1-nitropyrene, reduction to N-hydroxy-l-aminopyrene is a critical step in mutation induction. 

Certain nitro PAHs appear to require metabolism of their N-hydroxy arylamine derivatives in order to induce mutations. For example, while 2-nitrofluorene showed decreased mutagenicity in the nitroreductase-deficient mutant, TA98NR, and in strain TA98/1,8-DNP, its presumed ultimate mutagenic derivative, N-hydroxy-2-aminofluorene was inactive in only strain TA98/1,8-DNP (117). Observations such as these led McCoy t al. (117) to... 

Windmill KF, McKinnon RA, Zhu XY, Gaedigk A, Grant DM, Mcmanus ME. 1997. The role of xenobiotic metabolizing enzymes in arylamine toxicity and carcinogenesis—functional and localization studies. Mutat. Res. 376 153-60... 

Cascorbi I, Drakoulis N, BrockmoUer J, Maurer A, Sperling K, Roots I. Arylamine N-acetyltransferase (NAT2) mutations and their aUeUc linkage in unrelated Caucasian individuals correlation with phenotypic activity. Am J Hum Genet 1995 57 581-92. 

Yu MC, Ross RK (1998) Epidemiology of bladder cancer. In Petrovich Z, Baert L, Brady LW (eds) Carcinoma of the bladder. Innovations in management. Springer, Berlin, pp 1-13 Yu MC, Skipper PL, Tannenbaum SR, Chan KK, Ross RK (2002) Arylamine exposures and bladder cancer risk. Mutat Res/Fundam Mol Mech Mutagen 506-507 21-28. http //www.doi. org/10.1016/S0027-5107(02)00148-3... 

---