The major, N{sup 2}-Gua adduct of the (+)-anti-benzo[a]pyrene diol epoxide is capable of inducing G{yields}A and G{yields}C, in addition to G{yields}T, mutations

Journal Article · Tue Oct 17 04:00:00 EDT 1995 · Biochemistry (Eaton)

DOI:https://doi.org/10.1021/bi00041a034· OSTI ID:415157

Jelinsky, S A; Liu, T; Geacintov, N E ^[1]

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1. Boston Univ., MA (United States)

Mutations induced by the (+)-anti-diol epoxide of benzo[a]pyrene [(+)-anti-B[a]PDE] were collected in the supF gene of the Escherichia coli plasmid pUB3. pUB3 was reacted with (+)-anti-B[a]-PDE and then either (1) transformed immediately into E. coli or (2) heated at 80{degrees}C for 10 min and then cooled prior to transformation-the latter to probe mechanism. Qualitatively, heating did not affect the mutagenic pattern, except at the major base substitution hotspot in supF, G115, where principally G{yields}T mutations were obtained prior to heating, while after heating, G{yields}A and G{yields}C mutations became statistically significantly more prevalent. Several studies have suggested that a heat-induced chemical transformation of a (+)-anti-B[a]PDE adduct at G115 (e.g., into an apurinic site) is not likely to explain the change in mutational pattern. The most likely model is that (+)-anti-B[a]P-N{sup 2}-Gua is initially trapped in a metastable conformation giving principally G{yields}T mutations, while heating induces a change to a stable conformation(s) resulting in G{yields}T, A, and C mutations. This suggests that adduct conformational complexity is at the root of adduct mutational complexity. To investigate this model, a plasmid (B[a]P-G115-pRE1) with (+)-anti-B[a]P-N{sup 2}-Gua in the G115 sequence context is constructed using adduct site-specific techniques. Following transformations of B[a]P-G115-pRE1 into E. coli (ES87) cells, targeted G115{yields}T (59%), A (22%), and C (19%) mutations are isolated from (+)-anti-B[a]P-N{sup 2}-Gua, which approximates the ratio obtained at G115 with (+)-anti-B[a]PDE itself. (+)-anti-B[a]P-N{sup 2}-Gua principally induced G{yields}T mutations in another sequence context [5{prime}-TGC-3{prime}]. 35 refs., 4 figs., 1 tab.

• Sponsoring Organization: USDOE
• OSTI ID: 415157
• Journal Information: Biochemistry (Eaton), Journal Name: Biochemistry (Eaton) Journal Issue: 41 Vol. 34; ISSN 0006-2960; ISSN BICHAW
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
56 BIOLOGY AND MEDICINE
APPLIED STUDIES
BENZOPYRENE
CARCINOGENS
DNA
DNA ADDUCTS
EPOXIDES
ESCHERICHIA COLI
GENETIC EFFECTS
HEATING
METABOLITES
MUTATIONS