TY - JOUR
T1 - DNA damage and repair induced by diazoacetyl derivatives of amino acids with different mechanism of cytotoxicity. Correlations with mutagenicity and carcinogenicity
AU - Brambilla, G.
AU - Cavanna, M.
AU - Carlo, P.
AU - Finollo, R.
AU - Sciaba, L.
AU - Parodi, S.
AU - Bolognesi, C.
PY - 1979/1
Y1 - 1979/1
N2 - Eight synthetic N-diazoacetyl amino acids, prepared by inserting a diazoacetyl group onto the α-nitrogen of a natural amino acid, and two natural diazoazetyl amino acids, azaserine (O-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine), have been studied by autoradiography for their capacity to induce DNA repair synthesis in mouse cells cultivated "in vitro". Dose-dependent unscheduled DNA synthesis was present in cells treated with the eight N-diazoacetyl derivatives, and was absent in cells exposed to approximately equitoxic concentrations of azaserine and DON. Azaserine and DON, unlike N-diazoacetyl derivatives, did not alkylate γ-(4-nitrobenzyl) pyridine at an appreciable extent. When DNA damage (single stranded breaks or weak points in alkali) was measured by the sensitive technique of alkaline elution, DGA was found about 4 times as potent as azaserine and about 12 times as DON on a molar basis, but about 800 and 17,000 times as potent as azaserine and DON respectively by extrapolating to equitoxic concentrations. Carcinogenicity and mutagenicity seem to follow mainly the capability of inducing DNA damage.
AB - Eight synthetic N-diazoacetyl amino acids, prepared by inserting a diazoacetyl group onto the α-nitrogen of a natural amino acid, and two natural diazoazetyl amino acids, azaserine (O-diazoacetyl-L-serine) and DON (6-diazo-5-oxo-L-norleucine), have been studied by autoradiography for their capacity to induce DNA repair synthesis in mouse cells cultivated "in vitro". Dose-dependent unscheduled DNA synthesis was present in cells treated with the eight N-diazoacetyl derivatives, and was absent in cells exposed to approximately equitoxic concentrations of azaserine and DON. Azaserine and DON, unlike N-diazoacetyl derivatives, did not alkylate γ-(4-nitrobenzyl) pyridine at an appreciable extent. When DNA damage (single stranded breaks or weak points in alkali) was measured by the sensitive technique of alkaline elution, DGA was found about 4 times as potent as azaserine and about 12 times as DON on a molar basis, but about 800 and 17,000 times as potent as azaserine and DON respectively by extrapolating to equitoxic concentrations. Carcinogenicity and mutagenicity seem to follow mainly the capability of inducing DNA damage.
KW - Carcinogenicity
KW - Diazoacetyl amino acids
KW - DNA damage
KW - DNA repair
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U2 - 10.1007/BF00405345
DO - 10.1007/BF00405345
M3 - Article
C2 - 468901
AN - SCOPUS:0018345991
VL - 94
SP - 7
EP - 20
JO - Journal of Cancer Research and Clinical Oncology
JF - Journal of Cancer Research and Clinical Oncology
SN - 0171-5216
IS - 1
ER -