DNA adducts formation

Ni(salen)-DNA adduct formation is closely related to that formed by the Ni(peptide) systems, although there are different mechanisms proposed for both types of complexes. In the case of Ni(salen), the addition of a phenol radical to the guanine heterocycle and formation of a covalent bond to guanine C8 (Equation (9)) is suggested. 

No evidence of exposure-related DNA adduct formation in femur bone marrow, Zymbal gland, liver, or spleen was seen in rats treated orally with 75 mg/kg/day phenol for 4 days (Reddy et al. 1990). In this study, concurrent in vitro exposures of these tissues did produce adducts, suggesting that efficient detoxification and excretion mechanisms may be operating in vivo. 

La DK, Lilly PD, Anderegg RJ, et al DNA adduct formation in B6C3F1 mice and Fischer-344 rats exposed to 1,2,3-trichloropropane. Carcinogenesis 16(6) 1419-1424, 1995 

Direct evidence for the importance of DNA adduct formation being one 

Wilson PM, LA DK, Froines JR Hemoglobin and DNA adduct formation in Fischer-344 rats exposed to 2,4- and 2,6-toluene diamine. Arch Toxicol 70(10) 591-598, 1996 

A less invasive procedure that could provide a indication of DNA adduct formation is measurement in the urine of the mercaptic acid S-[2-N -guanl)ethyl]-N-acetylcysteine. Excretion of this metabolite into the urine of rats occurs in a dose-dependent, linear manner after intraperitoneal administration of 1,2-dibromoethane (Kim and Guengerich 1989). This biomarker has not been looked for to date in humans suspected to have exposure to 1,2-dibromoethane. 

Potter, G. A. McCague, R. Jarman, M. A mechanistic hypothesis for DNA adduct formation hy tamoxifen following hepatic oxidative metaholism. Carcinogenesis 1994,5, 439 142. 

Hayashi, N. Hasegawa, K. Barrett, J. C. Tsutsui, T. Estrogen-induced cell transformation and DNA adduct formation in cultured Syrian hamster embryo cells. Mol. Carcinog. 1996, 16, 149-156. 

Schehens JH, Ma J, Planting AS, et al. Relationship between the exposure to cisplatin, DNA-adduct formation in leukocytes and tumorresponse inpatients with sohd tumors. BrJ Cancer1996 73 1569-1575. 

Shellard SA, Fichtinger-Schepman AMJ, Lazo JS, Hill BT. Evidence of differential cisplatin DNA adduct formation, removal and tolerance of DNA damage in three human lung carcinoma cell lines. Anti-Cancer Drugs 1993 4 491-500. 

McElroy, A.E., J.M. Cahill, J.D. Sisson, and K.M. Kleinow. 1991. Relative bioavailability and DNA adduct formation of benzo[a]pyrene and metabolites in the diet of the winter flounder. Comp. Biochem. Physiol. 100C 29-32. 

I 97. Efarris, C. C. (1989). Interindividual variation. among humans in carcinogen metabolism, DNA adduct formation and DNA repair. Carcinogenesis 10, 1563-1566. 

Daniel FB, Schut HAJ, Sandwisch DW, et al Interspecies comparisons of benzo[ ]pyrene metabolism and DNA-adduct formation in cultmed human and animal bladder and tracheobronchial tissues. Cancer Res MAI 2M 4729, 1983 

Bodell, W. J. Ye, Q. Pathak, D. N. Pongracz, K. Oxidation of eugenol to form DNA adducts and 8-hydroxy-2 -deoxyguanosine role of quinone methide derivative in DNA adduct formation. Carcinogenesis 1998, 19, 437 143. 

Johnson SW, Shen DW, Pastan I, Gottesman MM, Hamilton TC. Cross-resistance, cisplatin accumulation and platinum-DNA adduct formation and removal in cisplatin-sensitive and -resistant human hepatoma cell lines. Exp Cell Res 1996 226 133-139. 

Dubois M, Pfohl-Leszkowicz A, De Waziers I, etal. 1996. Selective induction of the cyp3a family by endosulfan and DNA-adduct formation in different hepatic and hepatoma cells. Environmental Toxicology and Pharmacology l(4) 249-256. 

Fichtinger-Schepman AMJ, Dijt FJ, De Jong WH, van Oosterom AR, Berends F. In vivo cis-diamminedichloroplatinum(II)-DNA adduct formation and removal as measured with immunochemical techniques. In (Nicolini M, ed), Platinum and Other Metal Coordination Compounds in Cancer Chemotherapy 1988 Martinus Nijhoff Publishing Boston, pp. 32-46. 

Wen X, and Walle T (2005) Preferential induction of CYP1B1 by benzo[a]pyrene in human oral epithelial cells Impact on DNA adduct formation and prevention by polyphenols. Carcingenesis 26 1774—1781. 

In mice, also, deacetylation is involved in the hepato-carcinogenesis induced by 2-(acetylamino)fluorene. Indeed, BNPP-inhibited DNA-adduct formation in murine liver microsomes as well as tumor initiation by A-hydroxy-2-(acetylamino)fluorene in infant male B6C3Fj mice [100], 

Gupta-Burt S, Shamkhani H, Reed E, et al. Correlation between patient response in ovarian, breast, and colon cancer and platinum drug-DNA adduct formation. Cancer Epidem, Biomarkers Preven 1993 2 229-234. 

Apart from gene silencing, other effects of DNA methylation include spontaneous deamination, enhanced DNA binding of carcinogens and increased UV absorption by DNA, all of which increase the rate of mutations, DNA adduct formation and subsequent gene inactivation 

Jung KJ, Wallig MA and Singletary KW. 2006. Purple grape juice inhibits 7,12-dimethylbenz[a]anthracene (DMBA)-induced rat mammary tumorigenesis and in vivo DMBA-DNA adduct formation. Cancer Lett 233 279-288. 

Y. Ueyama, Y. Monden, X. B. He, C. X. Lin, M. A. Momen, S. Mimura and A. Umemoto, Effects of bile acids on 2-amino-1-methyl-6-phenylimidazo-[4,5-b]pyridine-induced aberrant crypt foci and DNA adduct formation in the rat colon, J. Exp. Clin. Cancer Res., 2002, 21, 577. 

Hypomethylation, as judged by loss of 5-methyl deoxycytidine content from DNA, occurred shortly after BaP exposure and continued upon termination of exposure conditions. Onset and persistence of hypomethylation were correlated with other types of DNA-damaging events, including strand breaks and DNA adduct formation 

Aflatoxin Bi (AFB) is a mold metabolite which has been observed to be acutely toxic and carcinogenic to a wide variety of animals (5,6) and has been implicated in human primary hepatic carcinoma (7, 8). Diets deficient in protein have been reported to increase the susceptibility of mammals to acute AFB toxicity and the induction of cancer (2, 9, 10, 11, 12, 13). Increased dietary proteins have increased the carcinogenic activity of AFB fed to rats (1 4) and trout (15.). Supportive of this latter finding has been the reported direct relationship between dietary protein content and AFB-DNA adduct formation in vivo in rats (16, 17). 

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