Biomedical subjects

J E Jablonski

Publications and source records attributed to J E Jablonski.

3 recordsLinked to original sources

PubMed1994

Data verification in the residue laboratory.

Residue analysis frequently presents a challenge to the quality assurance (QA) auditor due to the sheer volume of data to be audited. In the face of multiple boxes of raw data, some process must be defined that assures the scientist and the QA auditor of the quality and integrity of the data. A program that ensures that complete and appropriate verification of data before it reaches the Quality Assurance Unit (QAU) is presented. The "Guidelines for Peer Review of Data" were formulated by the Residue Analysis Business Center at Ricerca, Inc. to accommodate efficient use of review time and to define any uncertainties concerning what are acceptable data. The core of this program centers around five elements: Study initiation (definitional) meetings, calculations, verification, approval, and the use of a verification checklist.

Chemistry Techniques, Analytical↗

PubMed1986

Inhibition of the mutagenicity and metabolism of 6-methyl-benzo[a]pyrene and 6-hydroxymethyl-benzo[a]pyrene.

Previously reported inhibitors of benzo[a]pyrene (BaP) mutagenicity in Salmonella typhimurium strain TA98 were tested for their effectiveness against the mutagenicity of 6-methyl-benzo[a]pyrene (6-CH3-BaP), 6-hydroxymethyl-benzo[a]pyrene (6-CH2OH-BaP) and 6-acetoxymethyl-benzo[a]pyrene (6-CH3COOCH2-BaP). Dose-response curves obtained for phenothiazine (PTH), 2-chlorophenothiazine (2Cl-PTH), phenylisothiocyanate (PHN), phenethylisothiocyanate (PNE), trans-retinol (TR) and disulfiram (TETD) showed a variety of degrees of inhibition of mutagenicity. Additionally, glutathione (GSH) was found to inhibit the mutagenicity of 6-CH3COOCH2-BaP, and the mutagenicity of 6-CH2OH-BaP was enhanced by the addition of supplemental ATP, Na2SO4 and EDTA. Only 2Cl-PTH was equally as good an inhibitor of 6-CH3-BaP and BaP, reducing revertant colonies to less than 50% of control at 10 X BaP concentration. To probe the mechanism of inhibition, the effect of 2Cl-PTH on the binding of BaP and the 6-substituted benzo[a]pyrenes to cytochrome P-450 was investigated by difference spectroscopy. Also, the effect of 2Cl-PTH on the subsequent metabolism of 6-CH3-BaP and 6-CH2OH-BaP was investigated by rapid scan difference spectroscopy and high-performance liquid chromatographic separation of products. The results are consistent with a major mechanism of inhibition for 2Cl-PTH involving a competition for the cytochrome P-450 binding site.

Benzopyrenes↗

PubMed1986

Resorufin inhibits the in vitro metabolism and mutagenesis of benzo(a)pyrene.

7-Hydroxyphenoxazin-3-one, commonly known as resorufin, strongly inhibits benzo(a)pyrene-induced mutation in the Ames bacterial reversion assay. The antimutagenic mechanism is due in part to redox cycling of resorufin with the concommitant transfer of reducing equivalents from NADPH to molecular oxygen. The diversion of electrons from cytochrome P-450 enzymes results in a large decrease in the percent of benzo(a)pyrene metabolized by rat liver microsomes as measured by HPLC. Resorufin stimulated a non-stoichiometric consumption of NADPH and was reduced in S-9 or microsomal solutions. These processes were sensitive to dicumarol and NADP inhibition to different degrees in each liver fraction. This suggests two pathways are involved in resorufin redox cycling, one involving DT-diaphorase and the other with NADPH cytochrome P-450 reductase. Oxygen was shown to be an electron acceptor for S-9 mediated resorufin redox cycling, but was not consumed by a microsomal solution in the presence of resorufin and NADPH.

Animals↗