The Gln-Arg191 polymorphism of the human paraoxonase gene (HUMPONA) is not associated with the risk of coronary artery disease in Finns.

The human paraoxonase gene (HUMPONA) is codominantly expressed as alleles A and G. The A allele codes for glutamine (A genotype) and the G allele for arginine (B genotype) at position 191 of the paraoxonase enzyme. This genetic polymorphism has been suggested to be associated with the predisposition to coronary artery disease (CAD). We investigated the frequency of paraoxonase A and G alleles in 380 well-characterized CAD patients and in 169 controls. The most common genotype in both the patients with CAD (211/380) and in healthy Finnish individuals (87/169) was AA (Gln/Gln). The heterozygous AM (Gln/Arg) genotype was present in 140 of the patients and in 75 controls. The frequency of the A allele was 0.74 in both patients and controls. The genotype distribution between the two groups did not differ (P = 0.12, chi2 test). The genotype distributions were also similar to those reported earlier in other caucasoid populations. In conclusion, we found no association between the Gln-Arg 191 polymorphism of the human paraoxonase gene and coronary artery disease in Finns.

Human plasma phospholipid transfer protein causes high density lipoprotein conversion.

The effect of human plasma phospholipid transfer protein (PLTP) on the particle size distribution of human high density lipoprotein (HDL) was studied by incubating human HDL3 (particle diameter, 8.7 nm) together with PLTP in vitro. Incubation of HDL3 with highly purified preparations of PLTP, devoid of cholesterol ester transfer protein (CETP), induced a conversion of the homogenous population of HDL particles into two main populations of particles, one larger, particle diameter 10.9 nm, and one smaller, particle diameter 7.8 nm, than the original HDL3. These size changes were evident as analyzed by gradient gel electrophoresis and by high resolution gel filtration. The degree of the conversion was dependent on the amount of PLTP added to the incubation and on incubation time. An inhibitory monoclonal antibody (TP-1) directed against CETP had no effect on the HDL conversion. The PLTP used was purified to homogeneity from human plasma using ultracentrifugation and a combination of hydrophobic, cation-exchange, heparin-Sepharose-, anion-exchange, and gel filtration chromatographies. The monoclonal anti-CETP antibody (TP-1), which inhibits lipid transfer catalyzed by CETP, did not react with PLTP or inhibit its activity. The estimated molecular weight of PLTP is 75,000. The present study demonstrates that PLTP can act like the putative conversion factor and has the ability to convert HDL3 into populations of larger and smaller HDL particles. The mechanism(s) involved in this process and its physiological relevance remain to be established.

Mutagenicity of naphthacene, a non-bay-region aromatic hydrocarbon, in Salmonella.

Naphthacene (2,3-benzanthracene, tetracene) was tested for mutagenicity towards Salmonella typhimurium strains TA1535, TA1537, TA1538, TA98 and TA100. Mutagenicity was seen in all strains except in TA1535 when liver S9 fraction from rats or mice was present. The increases in the number of revertants induced by naphthacene equalled those by other naturally occurring polycyclic aromatic hydrocarbons, benzo[a]pyrene and dibenz[ac]anthracene, in the strains TA98 and TA100.

Mutagenicity studies of different polycyclic aromatic hydrocarbons: the significance of enzymatic factors and molecular structure.

Dependence of polycyclic aromatic hydrocarbon (PAH)-induced mutagenicity on the bay region of the molecule and on the activating cytochrome P-450 enzyme was studied. Eleven PAHs with and six without a bay region were activated by postmitochondrial supernatants from control and 3-methylcholanthrene (MC)-pretreated C57BL/6 mice and from control, MC- and 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-pretreated DBA/2 mice and from control and MC-pretreated Sprague-Dawley and Lewis rats. S-9 fractions from MC- or TCDD-treated animals induced more mutagenicity with PAHs with a bay region compared with S-9 fractions from control animals or MC-treated D2 mice. Mutagenicities of PAHs without a bay region were largely independent of the source of activating enzyme. There were three exceptions, namely benzo[e]pyrene, phenanthrene and perylene (each possessing a bay region), which were not mutagenic. These studies support the notion that the Ah-locus-controlled induction of cytochrome P1-450 activating PAHs into reactive intermediates at the bay region of the hydrocarbon molecule is of prime importance in the mutagenicity of PAHs. Qualitative correspondence to carcinogenicity is also apparent.

Absence of mutagenic activity of fodder proteins in the Ames Salmonella/microsome test.

The mutagenicities of fodder proteins (Pekilo, L-lysine and Orsan) were tested towards Salmonella typhimurium in the plate-incorporation assay in the presence or absence of metabolic activation with a rat-liver S9 preparation. Filtrates and 2-, 5- and 10-fold-concentrated filtrates of saline- or ethanol-soluble fodder proteins were tested. No mutagenic activity was observed.