Distribution of Initial and Persistent 2-acetylaminofluorene-induced DNA Adducts Within DNA Loops

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1985 Oct 1

PMID 3863117

Citations 4

Authors

R C Gupta

N R Dighe

K Randerath

H C Smith

Affiliations

Soon will be listed here.

Abstract

The intranuclear distribution of initial and persistent DNA adducts induced in vivo after four weekly injections of the hepatocarcinogen 2-acetylaminofluorene was examined in rat liver by using a protocol that fractionates chromatin from various regions of each of the multiple nuclear DNA loops. Ten hours after the initial dose, two acetylated [(N-acetyl-N-(deoxyguanosin-8-yl)-2-aminofluorene and 3-(deoxyguanosin-N2-yl)-2-acetylaminofluorene] and one deacetylated [N-(deoxyguanosin-8-yl)-2-aminofluorene] adduct were detected by a 32P-labeling assay and were found to have a random genomic distribution, as evident by their relative concentrations in various chromatin fractions. These data suggest that all regions of the DNA loops are equally susceptible to adduct formation. A nonrandom persistence of the deacetylated adduct in the regions where the DNA loops are constrained by the nuclear matrix was evident by 6 days after the last dose and was markedly apparent by 60 days. In contrast, all chromatin fractions had equally inefficient removal of the N2-acetylated adduct by 6 days as well as 60 days but had complete removal of the C8-acetylated adduct. These findings suggest that pronounced regional differences in adduct repair along the DNA loops may play a role in chemically induced hepatocarcinogenesis.

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References

Miller J . Carcinogenesis by chemicals: an overview--G. H. A. Clowes memorial lecture. Cancer Res. 1970; 30(3):559-76. View

Moyer G, Gumbiner B, Austin G . Binding of N-hydroxy acetylaminofluorene to eu- and heterochromatin fractions of rat liver in vivo. Cancer Lett. 1977; 2(4-5):259-65. DOI: 10.1016/s0304-3835(77)80030-x. View

Ramanathan R, Rajalakshmi S, SARMA D, Farber E . Nonrandom nature of in vivo methylation of dimethylnitrosamine and the subsequent removal of methylated products from rat liver chromatin DNA. Cancer Res. 1976; 36(6):2073-9. View

Finch J, Klug A . Solenoidal model for superstructure in chromatin. Proc Natl Acad Sci U S A. 1976; 73(6):1897-901. PMC: 430414. DOI: 10.1073/pnas.73.6.1897. View

Metzger G, Wilhelm F, Wilhelm M . Non-random binding of a chemical carcinogen to the DNA in chromatin. Biochem Biophys Res Commun. 1977; 75(3):703-10. DOI: 10.1016/0006-291x(77)91529-7. View

Miller E . Some current perspectives on chemical carcinogenesis in humans and experimental animals: Presidential Address. Cancer Res. 1978; 38(6):1479-96. View

Hemminki K, Vainio H . Preferential binding of benzo[a]pyrene into nuclear matrix fraction. Cancer Lett. 1979; 6(3):167-73. DOI: 10.1016/s0304-3835(79)80028-2. View

Walker M, Becker F, Rodriguez L . In vivo binding of N-2-acetylaminofluorene and its N-hydroxy derivative to the DNA of fractionated rat liver chromatin. Chem Biol Interact. 1979; 27(2-3):177-90. DOI: 10.1016/0009-2797(79)90124-8. View

Berezney R, Buchholtz L . Dynamic association of replicating DNA fragments with the nuclear matrix of regenerating liver. Exp Cell Res. 1981; 132(1):1-13. DOI: 10.1016/0014-4827(81)90076-8. View

10.

Smith H, Berezney R . DNA polymerase alpha is tightly bound to the nuclear matrix of actively replicating liver. Biochem Biophys Res Commun. 1980; 97(4):1541-7. DOI: 10.1016/s0006-291x(80)80041-6. View

11.

Schwartz E, Braselton Jr W, Goodman J . Factors influencing the binding of N-2-fluorenylacetamide to specific regions of the hepatic genome in vivo in rats. J Natl Cancer Inst. 1981; 66(4):667-72. View

12.

Ueyama H, Matsuura T, Nomi S, Nakayasu H, Ueda K . Binding of benzo(a)pyrene to rat liver nuclear matrix. Life Sci. 1981; 29(7):655-61. DOI: 10.1016/0024-3205(81)90017-5. View

13.

Basler J, Hastie N, Pietras D, Matsui S, Sandberg A, Berezney R . Hybridization of nuclear matrix attached deoxyribonucleic acid fragments. Biochemistry. 1981; 20(24):6921-9. DOI: 10.1021/bi00527a027. View

14.

Poirier M, True B, Laishes B . Formation and removal of (guan-8-yl)-DNA-2-acetylaminofluorene adducts in liver and kidney of male rats given dietary 2-acetylaminofluorene. Cancer Res. 1982; 42(4):1317-21. View

15.

Beland F, Dooley K, Jackson C . Persistence of DNA adducts in rat liver and kidney after multiple doses of the carcinogen N-hydroxy-2-acetylaminofluorene. Cancer Res. 1982; 42(4):1348-54. View

16.

Robinson S, Nelkin B, Vogelstein B . The ovalbumin gene is associated with the nuclear matrix of chicken oviduct cells. Cell. 1982; 28(1):99-106. DOI: 10.1016/0092-8674(82)90379-8. View

17.

Tabin C, Bradley S, Bargmann C, Weinberg R, Papageorge A, Scolnick E . Mechanism of activation of a human oncogene. Nature. 1982; 300(5888):143-9. DOI: 10.1038/300143a0. View

18.

Reddy E, Reynolds R, Santos E, Barbacid M . A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982; 300(5888):149-52. DOI: 10.1038/300149a0. View

19.

Beranek D, White G, Heflich R, Beland F . Aminofluorene-DNA adduct formation in Salmonella typhimurium exposed to the carcinogen N-hydroxy-2-acetylaminofluorene. Proc Natl Acad Sci U S A. 1982; 79(17):5175-8. PMC: 346857. DOI: 10.1073/pnas.79.17.5175. View

20.

Gupta R, Reddy M, Randerath K . 32P-postlabeling analysis of non-radioactive aromatic carcinogen--DNA adducts. Carcinogenesis. 1982; 3(9):1081-92. DOI: 10.1093/carcin/3.9.1081. View