Interaction of Chemical Carcinogens with Macromolecules

Overview

Journal J Cancer Res Clin Oncol

Specialty Oncology

Date 1981 Jan 1

PMID 7251633

Citations 10

Authors

P J OConnor

Affiliations

Soon will be listed here.

Abstract

The nature of certain critical cellular reactions is discussed in terms of both mutagenic and carcinogenic effects. Emphasis is placed on the ability of the ultimate carcinogen, normally formed in vivo by metabolism, to react with nucleic acids and, in particular, with nuclear DNA. The actions of N-nitroso compounds is examined in some detail and a possible correlation of the carcinogenic action of these compounds with their ability to react with oxygen-atoms in nucleic acids in considered. The formation of a specific lesion, O6-alkylguanine, in DNA and the capacity for its repair in different tissues is discussed with respect to tissue susceptibility to tumor induction. This discussion is extended to compare differences between species in the (tissue) specificity of action of particular N-nitroso compounds.

Citing Articles

Bracken Fern Carcinogen, Ptaquiloside, Forms a Guanine -Adduct in DNA.

Keskin F, Noone H, Dickman M, Allen E, Mulcrone W, Rasmussen L J Agric Food Chem. 2025; 73(2):1053-1061.

PMID: 39772526 PMC: 11741102. DOI: 10.1021/acs.jafc.4c07187.

Molecular origins of mutational spectra produced by the environmental carcinogen -nitrosodimethylamine and S1 chemotherapeutic agents.

Armijo A, Thongararm P, Fedeles B, Yau J, Kay J, Corrigan J NAR Cancer. 2023; 5(2):zcad015.

PMID: 36992846 PMC: 10041537. DOI: 10.1093/narcan/zcad015.

Animal Models: A Useful Tool to Unveil Metabolic Changes in Hepatocellular Carcinoma.

Serra M, Columbano A, Perra A, Kowalik M Cancers (Basel). 2020; 12(11).

PMID: 33182674 PMC: 7696782. DOI: 10.3390/cancers12113318.

Understanding the importance of low-molecular weight (ethylene oxide- and propylene oxide-induced) DNA adducts and mutations in risk assessment: Insights from 15 years of research and collaborative discussions.

Pottenger L, Boysen G, Brown K, Cadet J, Fuchs R, Johnson G Environ Mol Mutagen. 2018; 60(2):100-121.

PMID: 30536466 PMC: 6590209. DOI: 10.1002/em.22248.

Arabidopsis PARG1 is the key factor promoting cell survival among the enzymes regulating post-translational poly(ADP-ribosyl)ation.

Zhang H, Gu Z, Wu Q, Yang L, Liu C, Ma H Sci Rep. 2015; 5:15892.

PMID: 26516022 PMC: 4626836. DOI: 10.1038/srep15892.

References

Galbraith A, Barker M, Itzhaki R . Methylation of DNAase-digestible DNA and of RNA in chromatin from rats treated with dimethylnitrosamine. Biochim Biophys Acta. 1979; 561(2):334-44. DOI: 10.1016/0005-2787(79)90142-4. View

Lawley P, Orr D . Specific excision of methylation products from DNA of Escherichia coli treated with N-methyl-N'-nitro-N-nitrosoguanidine. Chem Biol Interact. 1970; 2(2):154-7. DOI: 10.1016/0009-2797(70)90047-5. View

Margison G, Swindell J, Ockey C, Craig A . The effects of a single dose of dimethylnitrosamine in the Chinese hamster and the persistence of DNA alkylation products in selected tissues. Carcinogenesis. 2012; 1(1):91-5. DOI: 10.1093/carcin/1.1.91. View

Montesano R, Bresil H, Margison G, Pegg A . Effect of chronic treatment of rats with dimethylnitrosamine on the removal of O6-methylguanine from DNA. Cancer Res. 1980; 40(2):452-8. View

Shooter K, Howse R, Shah S, Lawley P . The molecular basis for biological inactivation of nucleic acids. The action of methylating agents on the ribonucleic acid-containing bacteriophage R17. Biochem J. 1974; 137(2):303-12. PMC: 1166118. DOI: 10.1042/bj1370303. View

Lindahl T . DNA glycosylases, endonucleases for apurinic/apyrimidinic sites, and base excision-repair. Prog Nucleic Acid Res Mol Biol. 1979; 22:135-92. DOI: 10.1016/s0079-6603(08)60800-4. View

Kleihues P, Margison G . Carcinogenicity of N-methyl-N-nitrosourea: possible role of excision repair of O6-methylguanine from DNA. J Natl Cancer Inst. 1974; 53(6):1839-41. View

Swann P, MAGEE P . Nitrosamine-induced carcinogenesis. The alkylation of N-7 of guanine of nucleic acids of the rat by diethylnitrosamine, N-ethyl-N-nitrosourea and ethyl methanesulphonate. Biochem J. 1971; 125(3):841-7. PMC: 1178189. DOI: 10.1042/bj1250841. View

Margison G, Margison J, Montesano R . Accumulation of O6-methylguanine in non-target-tissue deoxyribonucleic acid during chronic administration of dimethylnitrosamine. Biochem J. 1977; 165(3):463-8. PMC: 1164928. DOI: 10.1042/bj1650463. View

10.

Dipple A, Brookes P, Mackintosh D, Rayman M . Reaction of 7-bromomethylbenz(a)anthracene with nucleic acids, polynucleotides, and nucleosides. Biochemistry. 1971; 10(23):4323-30. DOI: 10.1021/bi00799a026. View

11.

Cox R, IRVING C . O6-methylguanine accumulates in DNA of mammary glands after administration of N-methyl-N-nitrosourea to rats. Cancer Lett. 1979; 6(4-5):273-8. DOI: 10.1016/s0304-3835(79)80045-2. View

12.

Kleihues P, Bucheler J . Long-term persistence of O6-methylguanine in rat brain DNA. Nature. 1977; 269(5629):625-6. DOI: 10.1038/269625a0. View

13.

Wislocki P, Borchert P, Miller J, Miller E . The metabolic activation of the carcinogen 1'-hydroxysafrole in vivo and in vitro and the electrophilic reactivities of possible ultimate carcinogens. Cancer Res. 1976; 36(5):1686-95. View

14.

DOLL R . Strategy for detection of cancer hazards to man. Nature. 1977; 265(5595):589-96. DOI: 10.1038/265589a0. View

15.

Margison G, Kleihues P . Chemical carcinogenesis in the nervous system. Preferential accumulation of O6-methylguanine in rat brain deoxyribonucleic acid during repetitive administration of N-methyl-N-nitrosourea. Biochem J. 1975; 148(3):521-5. PMC: 1165571. DOI: 10.1042/bj1480521. View

16.

Ames B, McCann J, Yamasaki E . Methods for detecting carcinogens and mutagens with the Salmonella/mammalian-microsome mutagenicity test. Mutat Res. 1975; 31(6):347-64. DOI: 10.1016/0165-1161(75)90046-1. View

17.

COOPER H, Hauenstein E, KOLAR G, Kleihues P . DNA alkylation and neuro-oncogenesis by 3,3-dimethyl-1-phenyltriazene. Acta Neuropathol. 1978; 43(1-2):105-9. DOI: 10.1007/BF00685004. View

18.

Robins P, Cairns J . Quantitation of the adaptive response to alkylating agents. Nature. 1979; 280(5717):74-6. DOI: 10.1038/280074a0. View

19.

COOPER H, Buecheler J, Kleihues P . DNA alkylation in mice with genetically different susceptibility to 1,2-dimethylhydrazine-induced colon carcinogenesis. Cancer Res. 1978; 38(9):3063-5. View

20.

Pegg A . Alkylation of rat liver DNA by dimethylnitrosamine: effect of dosage on O6-methylguanine levels. J Natl Cancer Inst. 1977; 58(3):681-7. DOI: 10.1093/jnci/58.3.681. View