1987
DOI: 10.1073/pnas.84.2.344
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DNA base changes and alkylation following in vivo exposure of Escherichia coli to N-methyl-N-nitrosourea or N-ethyl-N-nitrosourea.

Abstract: Dideoxy chain-termination DNA sequencing was used to determine the specific DNA base changes induced after in vivo exposure of Escherichia coli to N-methyl-Nnitrosourea (MNU) and N-ethyl-N-nitrosourea (ENU) using the xanthine guanine phosphoribosyltransferase (gpt) gene as the genetic target. The resultant mutation spectra were compared with the levels of O6-alkylguanine and 04-alkylthymidine in genomic DNA immediately after exposure. All (39/39) of the MNU-induced mutations were G-C-+A-T transitions. In contr… Show more

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Cited by 196 publications
(104 citation statements)
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“…For instance, it could direct the search for carcinogens present in the diet or in cigarette smoke. The similarities in the spectra of ras mutations found in lung tumors and those induced by aromatic hydrocarbons such as benzopyrene (47) and in gastrointestinal tumors with those induced by alkylating agents such as methylnitrosourea (48) are certainly very suggestive.…”
Section: Discussionmentioning
confidence: 92%
“…For instance, it could direct the search for carcinogens present in the diet or in cigarette smoke. The similarities in the spectra of ras mutations found in lung tumors and those induced by aromatic hydrocarbons such as benzopyrene (47) and in gastrointestinal tumors with those induced by alkylating agents such as methylnitrosourea (48) are certainly very suggestive.…”
Section: Discussionmentioning
confidence: 92%
“…These di erences might be related to the type of induced genetic alteration. While MNU usually produces point mutations and alkylation in the DNA (Richardson et al, 1987), radiation can cause di erent kinds of DNA damage, including base alterations, deletions, insertions and internal rearrangements (Hutchinson, 1985). In concordance with this, although g-radiation-induced lymphomas are frequently deleted in a chromosome 4 region named TLSR1, no LOH in this region has been found in tumors induced by MNU treatment (Santos et al, 1996).…”
Section: Mouse P15 Ink4b and P16 Ink4a Cpg Islands Are Hypermethylatementioning
confidence: 93%
“…At both loci, the incidence and the location of GC4AT transitions are consistent with the hypothesis that O6-alkylguanine is the main determinant of CCNU mutagenicity. Alkylnitrosoureas preferentially cause GC4AT transitions at Gs preceded by a Pu residue in E. coli (Jurado et al, 1995;RoldaÁ n-Arjona et al, 1994;Richardson et al, 1987;Burns et al, 1988) and in eukaryotes (Inga et al, 1995;Kunz and Mis, 1989;Minnick et al, 1992;Moriwaki et al, 1991;Palombo et al, 1992). The 5'-¯anking purine eect has been explained as the consequence of a structural in¯uence on the initial formation of O6-alkylguanine, which may be further enhanced by alkylation speci®c repair (Horsfall et al, 1990).…”
Section: Discussionmentioning
confidence: 99%