Chemical Carcinogenesis: Models and Mechanisms by Harry V. Gelboin, Frank J. Gonzalez, Sang S. Park, Junji

By Harry V. Gelboin, Frank J. Gonzalez, Sang S. Park, Junji Sagara, Narayana Battula (auth.), Francesco Feo, Paolo Pani, Amedeo Columbano, Renato Garcea (eds.)

About centuries after the verbal exchange via Sir Percival Pott that the "chimney sweeper ailment" used to be a melanoma and its recommendation that lively compounds of soot have been the causative brokers, and approximately one century after the outline of urinary bladder melanoma in dye staff, an immense variety of ingredients were synthesized and feature most likely come into touch with guy. examine in melanoma prevention is of fundamental significance, and should obtain non-stop aid from new discoveries on melanoma etiology and pathogenesis. If one accepts the multistage version of chemical carcinogenesis, one has additionally to simply accept that many occasions happen among the touch of carcino­ genic compounds and their particular ambitions and the advance of a clinically recognizable neoplasm. hence, animal stories develop into necessary to elucidate different steps through which chemical cancer agents set off neoplasia. The research of those steps and the comparative evaluate of experimental versions is vital to an figuring out of pathogenesis.

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MS1 M1 MS2 M2 MS3 Identification of BaP-DNA Adducts Formed in Cell Cultures Unidentified BaP-metabolite-adduct; not (-)-anti-BaPDE-dG (-)-Syn-BaPDE-dG (+)-Anti-BaPDE-dG (+)-Syn-BaPDE-dG Syn-BaPDE-adduct breakdown product (7,9,10/8-tetraol) The BaP-deoxyribonucleoside adduct profiles and the methods used for their analysis are described in Fig. 2. 29 • 90 SYRIAN HAMSTER EMBRYO • c IoU 70 • N :; SENCAR MOUSE EMBRYO RAINBOII TROUT 0 '" IC( • IoU %: • .... ,.. BROlIN BULLHEAD BLUEGILL FRY 50 • IIISTAR RAT EMBRYO 30 10 10 30 50 70 90 PMOLE B(a)P-DNA ADDUCTS/mg DNA Fig.

ACKNOWLEDGEMENTS The authors wish to acknowledge the technical assistance provided by Stephanie Morgan, Mark Ferin, Connie Moynihan and Cyndy Salmon and thank Marilyn Hines for typing the manuscript. This work was supported by PHS grants CA28825 and CA40228 from the National Cancer Institute, DHHS. 24 TIllE OF B(a)P UPOSURE (HR) ~ 5 WISTAR RAT rlZj FISHER RAT 48 w n. SYRIAN HAMSTER >~ -' -' ~ SEN CAR MOUSE BALB/c MOUSE BLUEGILL FRY o w w ~ ~ ~ ~ ro ~ ~ ~ % OF (+) - ANTI - B(a)PDE ADDUCT Fig. 9.

1985). S. Thorgeirsson, D. J. Jollow, H. A. Sasame I. Green, and J. R. Mitchell, The role of cytochrome P-450 in N-hydroxylation of 2-acetylaminofluorene, Mol. Pharmacol. 9:398-404 (1973). F. Kadlubar, J. A. Miller and E. C. Miller, Microsomal N-oxidation of the hepatocarcinogen N-methyl-4-aminoazobenzene and the reactivity of N-hydroxy-N-methyl-4-aminoazobenzene, Cancer Res. 36:1196 (1976). ---P. Guengerich, Enzymology of rat liver cytochromes P-450, in: "Mammalian Cytochromes P-450", Vol. I, CRC Press, Boca Raton, FL (1985).

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