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Related Experiment Videos

N6-(Methylnitroso)adenosine: a carcinogen from a nucleic acid component

A Giner-Sorolla, L M Anderson, J H Greenbaum

    IARC Scientific Publications
    |January 1, 1980
    PubMed
    Summary

    Nitrosation of N6-methyladenosine can form a carcinogen, N6-(methylnitroso)adenosine (m6(NO)Ado). This compound induced tumors in mice, including reproductive system neoplasms, an unusual target for N-nitroso carcinogens.

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    Area of Science:

    • Biochemistry
    • Toxicology
    • Carcinogenesis

    Background:

    • Substituted aminopurines can form carcinogenic nitrosaminopurines via nitrosation.
    • Gastric conditions can promote the nitrosation of N6-methyladenosine.

    Purpose of the Study:

    • To investigate the carcinogenic potential of N6-(methylnitroso)adenosine (m6(NO)Ado).
    • To determine the in vivo formation of carcinogens from N6-methyladenosine and nitrite.
    • To identify tumor types and target organs induced by m6(NO)Ado.

    Main Methods:

    • Nitrosation of N6-methyladenosine under simulated gastric conditions.
    • Parenteral and oral administration of m6(NO)Ado to mice.
    • Administration of precursors (m6Ado and nitrite) and the nitrosamine base (N6-(methylnitroso)-adenine) to mice.

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  • In vitro inhibition studies using ascorbic acid.

    • Main Results:

    • Parenteral m6(NO)Ado induced thymic lymphomas, lung adenomas, and liver tumors in young mice.
    • Oral m6(NO)Ado induced reproductive system tumors in 80% of female mice and lung tumors in both sexes.
    • Combined precursors (m6Ado and nitrite) increased lung tumors in male mice.
    • N6-(methylnitroso)-adenine was less potent, causing lung tumors in males and possibly mammary tumors in females.
    • Ascorbic acid completely inhibited nitrosaminopurine formation in vitro.

    Conclusions:

    • N6-methyladenosine and nitrite can form an in vivo carcinogen, m6(NO)Ado.
    • m6(NO)Ado is a potent carcinogen, inducing neoplasms in the reproductive system, an unusual target.
    • Ascorbic acid can prevent the formation of these carcinogenic nitrosopurines.