Complete cDNA sequence of the Ki-ras proto-oncogene in the liver of wild English sole (Pleuronectes vetulus) and mutation analysis of hepatic neoplasms and other toxicopathic liver lesions.

A complete copy of Ki-ras b cDNA from English sole (Pleuronectes vetulus), a benthic marine flatfish, was cloned and sequenced. The percent identity between the predicted amino acid sequence of English sole and human Ki-ras b was 97%, whereas the percent identity between the English sole gene and rainbow trout or Rivulus Ki-ras b was 98%. Areas of amino-acid sequence conservation included codons 12, 13, and 61, the positions in which mutations are observed in ras cellular oncogenes in other species.

Molecular epizootiology of genotoxic events in marine fish: linking contaminant exposure, DNA damage, and tissue-level alterations.

Molecular epizootiological studies are increasingly being used to investigate environmental effects of genotoxic contaminants. The assessment of damage to DNA and linking the damage to subsequent molecular, cellular, or tissue-level alterations is a central component of such studies. Our research has focused on the refinement of the 32P-postlabeling assay for measuring covalent DNA-xenobiotic adducts arising from exposure to polycyclic aromatic compounds, using DNA adducts as molecular dosimeters of genotoxic contaminant exposure in biomonitoring studies, and investigating the relationship of DNA adduct formation to toxicopathic liver disease, including neoplastic lesions.

Structure-activity analysis of the antitumor and hemolytic properties of the amphiphilic alpha-helical peptide, C18G.

The in vitro antitumor and hemolytic activities of analogs of peptide C18G were compared in order to elucidate important structural features which affect cytotoxicity. The sequence of C18G, a basic peptide which can form an amphiphilic alpha-helix, is a derivative of the carboxyl terminus of human platelet factor IV. The results demonstrate that both amphiphilicity and helicity are essential for peptide activity, and that addition of a negatively charged amino acid results in decreased cell lysis.

Identification of serum components that inhibit the tumoricidal activity of amphiphilic alpha helical peptides.

Antimicrobial peptides that can form amphiphilic alpha helices were tested for their ability to lyse various human tumor cell lines in vitro. These peptides include C18G, whose sequence is a derivative of the carboxyl terminus of human platelet factor IV, and 399, an idealized amphiphilic alpha helix. Both peptides exhibited potent antitumor activity against all cell lines tested, unlike magainin 2, a naturally occurring antimicrobial peptide of similar structure, which was relatively inactive under the same conditions.

Kinetics of the processing of the precursor to 4.5 S RNA, a naturally occurring substrate for RNase P from Escherichia coli.

A study was made of the cleavage by M1 RNA and RNase P of a non-tRNA precursor that can serve as a substrate for RNase P from Escherichia coli, namely, the precursor to 4.5 S RNA (p4.5S).