Sp Lesions Research Articles

Removal of hydantoin products of 8-oxoguanine oxidation by the Escherichia coli DNA repair enzyme, FPG.

An intriguing feature of 7,8-dihydro-8-oxo-2'-deoxyguanosine (OG) is that it is highly reactive toward further oxidation. Indeed, OG has been shown to be a "hot spot" for oxidative damage and susceptible to oxidation by a variety of cellular oxidants. Recent work has identified two new DNA lesions, guanidinohydantoin (Gh) and spiroiminodihydantoin (Sp), resulting from one-electron oxidation of OG. The presence of Gh and Sp lesions in DNA templates has been shown to result in misinsertion of G and A by DNA polymerases, and therefore, both are potentially mutagenic DNA lesions. The base excision repair (BER) glycosylases Fpg and MutY serve to prevent mutations associated with OG in Escherichia coli, and therefore, we have investigated the ability of these two enzymes to process DNA duplex substrates containing the further oxidized OG lesions, Gh and Sp. The Fpg protein, which removes OG and a variety of other oxidized purine base lesions, was found to remove Gh and Sp efficiently opposite all four of the natural DNA bases. The intrinsic rate of damaged base excision by Fpg was measured under single-turnover conditions and was found to be highly dependent upon the identity of the base opposite the OG, Gh, or Sp lesion; as expected, OG is removed more readily from an OG:C- than an OG:A-containing substrate. However, when adenine is paired with Gh or Sp, the rate of removal of these damaged lesions by Fpg was significantly increased relative to the rate of removal of OG from an OG:A mismatch. The adenine glycosylase MutY, which removes misincorporated A residues from OG:A mismatches, is unable to remove A paired with Gh or Sp. Thus, the activity of Fpg on Gh and Sp lesions may dramatically influence their mutagenic potential. This work suggests that, in addition to OG, oxidative products resulting from further oxidation of OG should be considered when evaluating oxidative DNA damage and its associated effects on DNA mutagenesis.

Incidence of tonsillar lesions caused by Tonsillophilus suis and Actinomyces sp infection in swine.

The tonsils of ten fattening pigs were compared with those of ten breeding sows to determine the relative incidence of Tonsillophilus suis and Actinomyces sp lesions. Macroscopic observation revealed mildly focal upheavals on the tonsillar mucosal surfaces of two of the breeding sows. In tonsillar slices from both pig groups, tiny nodules containing sulfur granules were found. Histopathologically, the T. suis and Actinomyces sp lesions were noted as tonsillar crypt abscesses in both pig groups, and granulomas due to T. suis were seen in the breeding sows. T. suis showed larger 'club-shaped' structures than Actinomyces sp, characterized as clubs showing a broom-like structure with degenerated central thalli. Breeding sows are known to have a higher incidence of tonsillar T. suis lesions than fattening pigs, and in this study, those fattening pigs showing greater propensity to infection by Actinomyces sp also showed a mixed infection with T. suis that produced the tonsillar crypt abscesses. In addition, it is known that in breeding sows, the T. suis lesion develops from a crypt abscess into a granuloma.