Comutagenic effect

Umezawa, K. Shirai, A. Matsushima, T. Sugimura, T. 1978. Comutagenic effect of norharman and barman with 2-acetyl-aminofluorene derivatives. Proceedings of the National Academy of Sciences Vol. 75 928-930. 

Schwartz JL, Morgan WF, Brown-Lindquist P, Afzal V, Weichselbaum RR, Wolff S (1985) Comutagenic effects of 3-aminobenzamide in Chinese hamster ovary cells. Cancer Res 45 1556-1559... 

Compounds of antimony have not been assayed for mutagenicity in mammalian cells. Sb(III) was shown to enhance transformation by SA7 virus (Casio et al. 1979). Because antimonite resembles arsenite, and can induce arsenite tolerance (Wang and Rossman 1993), one might speculate that antimonite could have a comutagenic effect similar to that of arsenite. 

Substitution of Mn(II) for Mg(II) in DNA polymerases results in decreased fidelity (Goodman et al. 1983 Beckman et al. 1985). Under conditions where Mn(II) is not mutagenic, it enhanced UV-induced mutagenesis in E. coli (Rossman and Molina 1986). A likely explanation for the comutagenic effect is that Mn(II) affects DNA replication of a damaged template. This was shown in the case of alkylation damage, where Mn(II) facilitated postlesion synthesis which was accompanied by misincorporation opposite the alkylated bases (Bhanot and Solomon 1994). 

Okui T, Fujiwara Y (1986) Inhibition of human excision DNA repair by inorganic arsenic and the comutagenic effect in V79 Chinese hamster cells. Mutat Res 172 69-76... 

Rossman TG (1989) On the mechanism of the comutagenic effect of Cu(II) with ultraviolet light. Biol Trace Elem Res 21 383-388 Rossman TG, Molina M (1986) The genetic toxicology of metal compounds. II. Enhancement of ultraviolet light-induced mutagenesis in E. coli WP2. Environ Mutagen 8 263-271... 

FIGURE 6. Comutagenic effects of norharman on aniline mutagenesis using strain TA98 with PCB-treated rat liver S-9 Mix. (a) Norharman was added at 200 g/tube in the preincubation mixture with various doses of aniline, (b) Effects of various amounts of S-9 50 /xg aniline and 200 fjLg norharman were used, (c) Effects of various amounts of norharman 50 g aniline and 70 1 S-9 were used. ( ) With norharman (O) without norharman. 

K. Umezawa, A. Shiri, T. Matsushima, and T. Sugimura, Comutagenic effect of norharman and barman with 2-acetylaminofluorene derivatives Salmonella typhimurium/xmcTosomd enzymes/carcinogens, Proc. Natl. Acad. Sci. U.S.A. 75, 928-930 (1978). 

Vogt, B. L. and Rossman, T. G., Effects of arsenite on p53, p21 and cyclin D expression in normal human fibroblasts—a possible mechanism for arsenite s comutagenicity, Mutat. Res., 478, 159, 2001. 

Life Sci 1991 48(12) 1173-1177. Crebelli, R., L. Conti, S. Fuselli, P. Leopardi, A. Zijno, and A. Carere. Put-ther studies on the comutagenic activity of cigarette smoke condensate. Mutat Res 1991 259(1) 29-36. Padma, P. R., A. J. Amonkar, and S. V. Bhide. Effect of long-term treatment of two tobacco-specific N-nitro-samines on the vitamin A status of mice. Nutr Cancer 1991 15(3—4) 217-220. 

Balanski RM. 1991. Comutagenic and coclastogenic effects of selenium in vitro and in vivo. Mutat Res 263(4) 231-236. 

The enhancement or inhibitory effect of the comutagens on mutagenicity may be a net result of substrate inhibition and membrane fluidization in the microsomal or nuclear mixed-function-oxidase system. 

Comutagenic Action of Harman and Norharman When the reconstituted MFO system, which contained 3-MC induced cytochrome P-448, was used to study the effects of Norharman and Harman on the hydroxylation of Benzo(a)pyrene, they both showed an enhancement effect under the optimal enzymatic conditions. Norharman, however, showed a larger activity increase in Benzo(a)pyrene hydroxylation than Harman(Figure 5). It ascertains that the inhibitory effects of these carbolines on mutagenicity are not dependent on cytochrome P-448 in the sense of simple substrate inhibition. 

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