Potential molecular mechanisms of oxidant-induced carcinogenesis.

Abstract:

:Chronic exposure to oxidants is associated with an increased incidence of malignancy; however, the mechanism(s) by which oxidants contribute to carcinogenesis is unknown. Since oncogene activation plays an important role in carcinogenesis, we hypothesized that hydroxyl radical-induced DNA damage might contribute to carcinogenesis by causing oncogene activation. The studies reported herein demonstrate that hydroxyl radical-induced DNA damage can activate the K-ras 4B and C-Raf-l oncogenes by causing point mutations and deletions, respectively. In addition, our results indicate that a) hydroxyl radical-induced DNA damage causes selective base substitutions; b) the four DNA bases have different susceptibilities to hydroxyl radical-induced mutations; and c) hydroxyl radical-induced mutations are not randomly distributed among oncogene codons. Our studies suggest that oncogene activation could be one potential mechanism by which oxidants contribute to carcinogenesis.

authors

Jackson JH

doi

10.1289/ehp.94102s10155

subject

Has Abstract

pub_date

1994-12-01 00:00:00

pages

155-7

eissn

0091-6765

issn

1552-9924

journal_volume

102 Suppl 10

pub_type

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