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P S Magee

Publications and source records attributed to P S Magee.

6 recordsLinked to original sources
PubMed2000

The tumorigenicity of mutagenic contact-sensitizing chemicals.

The electrophilic nature of some contact sensitizers, that is, chemicals that cause allergic contact dermatitis (ACD), is also characteristic of genotoxic tumorigens. Electrophiles can adduct protein, which is the basis for ACD, as well as DNA, which is the basis for mutagenicity and carcinogenicity. This suggests that some electrophilic contact sensitizers may be genotoxic tumorigens. To further investigate this matter, we evaluated 146 chemicals that had been bioassayed for tumorigenicity and mutagenicity in the National Toxicology Program, with an analysis of structure-activity relationships for contact sensitization. Using the data from this analysis and from other sources, the proportion of the contact sensitizers that were both mutagenic and tumorigenic was found to range from 20% to 28%. This finding suggests that there may be in the order of 90 genotoxic tumorigens for rodents among the approximately 384 chemicals that have been validated as contact sensitizers for humans.

Animals↗
PubMed1995

A local lymph-node assay validation study of a structure-activity relationship model for contact allergens.

A structure-activity relationship model for prediction of contact allergenic potential of chemicals had previously been developed. The model had been shown to be able to classify known allergens and nonallergens using data on physicochemical and reactivity parameters of functional groups by discriminant two-value multiple regression analysis. To investigate the model, six selected chemicals which had not been previously investigated for allergenicity were studied with both the model and a murine local lymph-node assay. The same compounds were predicted to be allergens (3-bromo-2-coumaranone, 1-nitrocyclohexene and alpha-acryloyloxy-beta, beta-dimethyl-beta-butyrolactone) and nonallergens (1-carbethoxy-4-piperidone, 6,7-dimethoxy-2-tetralone and 9-acetylanthracene) by both the model and the local lymph-node assay.

Allergens↗
PubMed1991

Complex factors in hydrocarbon/water, soil/water and fish/water partitioning.

Many partitioning and toxicological events that appear to correlate simply with log P (octanol/water) can be resolved into greater detail by a factoring process. Log P can be separated into lipophilic (PL) and hydrophilic (PH) contributions that combine well with polarizability (MR) and hydrogen-bonding (HB) to describe partitioning and non-specific binding in phases that differ greatly from n-octanol. In addition, hydrogen-bonding can be factored into donor groups (HBD) and acceptor groups (HBA) for stronger correlations and greater mechanistic insight. These descriptors are applied to a variety of problems in simple partitioning, soil organic matter binding, bioaccumulation in fish, and aquatic narcosis and toxicity.

Animals↗
PubMed1986

Synthesis and evaluation of phenyl- and benzoylpiperazines as potential serotonergic agents.

The binding of a series of phenylpiperazines (3) and benzoylpiperazines (4) to central serotonin (5-HT) sites was investigated. Several derivatives of 3 displayed nanomolar affinities for 5-HT1 sites, whereas derivatives of 4 were essentially inactive both at 5-HT1 and 5-HT2 sites. 1-(2-Methoxyphenyl)piperazine (2-MPP, 3a) was found to possess an affinity (Ki = 35 nM) for 5-HT1 sites comparable to that of the recognized 5-HT agonist 1-[3-(trifluoromethyl)phenyl]piperazine (TFMPP) (Ki = 20 nM); 3a also displayed a 100-fold selectivity for 5-HT1 sites (as compared to 8-fold for TFMPP). In tests of stimulus generalization using rats trained to discriminate TFMPP (ED50 = 0.17 mg/kg) from saline, 3a was found to be nearly equipotent (ED50 = 0.22 mg/kg) with the training drug. These results suggest that 3a may be a novel and more selective 5-HT1 agonist than TFMPP.

Animals↗