Background: Several genome duplications have occurred in the evolutionary history of teleost fish. In returning to a stable diploid state, the polyploid genome reorganized, and large portions are lost, while the fish lines evolved to numerous species. Large scale transposon movement has been postulated to play an important role in the genome reorganization process. We analyzed the DNA sequence of several large loci in Salmo salar and other species for the presence of DNA transposon families.

The relative role of point mutations and large genomic rearrangements in ionizing radiation-induced mutagenesis has been an issue of long-standing interest. Recent studies using Southern blotting analysis permit the partitioning of ionizing radiation-induced mutagenesis in mammalian cells into detectable deletions and major genomic rearrangements and into point mutations. The molecular nature of these point mutations has been left unresolved; they may include base substitutions as well as small deletions, insertions, and frameshifts below the level of resolution of Southern blotting analysis. In this investigation, we have characterized a collection of ionizing radiation-induced point mutations at the endogenous adenine phosphoribosyltransferase (aprt) locus of Chinese hamster ovary cells at the DNA sequence level. Base substitutions represented =2/3 of the point mutations analyzed. Although the collection of mutants is relatively small, every possible type of base substitution event has been recovered. These mutations are well distributed throughout the coding sequence with only one multiple occurrence. Small deletions represented the remainder of characterized mutants; no insertions have been observed. Sequence-directed mechanisms mediated by direct repeats could account for some of the observed deletions, while others appear to be directly attributable to radiation-induced strand breakage.Although ionizing radiation was the first known mutagen (1), relatively little is known about the molecular mechanisms of ionizing radiation-induced mutagenesis in mammalian cells.

The in vivo production of frameshift and base-substitution mutations predicted as a consequence of the metabolic processing of misaligned quasipalindromic DNA sequences has been confirmed. Spontaneous frameshift mutations of the T4 Wi gene that had been genetically mapped to quasipalindromic DNA sequences were sequenced. Some of the mutant sequences are exactly those predicted by a mutational model based on misaligned quasipalindromes. Furthermore, these sequences are distinct from those predicted by the classical frameshift model based on misaligned repeated sequences. The ilI frameshift mutant sequences reported here result from the deletion of a specific base or bases that would remain looped out should the quasipalindromes assume a hairpin secondary structure. One hairpin predicted not only the deletion of two bases (a frameshift) but the concomitant production of nearby but noncontiguous base substitutions. The substitution of as many as three bases as well as the frameshift were predicted to arise as a consequence of a single mutational event in the palindrome. Two independent examples of the predicted deletion frameshift were found among the small sample of sequenced spontaneous frameshifts examined and both were associated with the predicted transversion and transition base substitutions.Frameshift mutations often result from the addition or deletion of a repeating unit of a repeated DNA sequence. Metabolic processing of misaligned pairing between one of the repeating units and the complement of another is believed to be responsible (1, 2). However, frameshifts can occur in DNA sequences that are not repeated. A consideration of molecular mechanisms responsible for these mutations led to the proposal that some frameshifts occur because of processing of misaligned pairing mediated by quasipalindromes (3-5).Palindromic sequences permit the formation of alternative DNA secondary structures such as DNA hairpins. The action of ordinary DNA metabolism on such structures is predicted to lead to mutation (3, 5). The demonstration of mutations predicted to occur as a consequence of such processing and not by other mutational models would be strong confirmation of the quasipalindrome mutational model and would suggest the occurrence of palindromically mediated misalignments in vivo.Quasipalindromes permit the formation of misaligned structures through the self-complementarity of their palindromic portions and provide templates for base-substitution and frameshift mutations in their nonpalindromic portions (3). Mutations are predicted to result from templated processes that replace bases residing in one half of the hairpin with bases complementary to the other half. The predicted mutations can be readily visualized by examining quasipalindromic DNA sequences in hairpin structures (Fig. 1). Each unpaired base in the stem of the hairpin lacks a complemen-

A limited number of randomized controlled trials were identified in which diet and dietary supplement interventions appeared to slow disease progression in men with prostate cancer, although results vary. Studies were limited by reliance on the surrogate biomarker prostate specific antigen, sample size and study duration. Well designed trials are warranted to expand knowledge, replicate findings and further assess the impact of diet and dietary supplement interventions on recurrence and treatment associated morbidities.

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