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Biomedical subjects

B Paigen

Publications and source records attributed to B Paigen.

105 records · Page 6Linked to original sources
PubMed1978

Aryl hydrocarbon hydroxylase in persons with lung or laryngeal cancer.

To test whether the distribution of AHH inducibility is shifted toward the high end of the range in patients who had lung and laryngeal cancer, we measured this trait in 59 patients (32 lung and 27 laryngeal) who had resectable tumors and had been disease-free for a period of time. The advantage of selecting patients who were free of clinical disease was that measurement of their AHH inducibility should not have been affected by the disease state. Patient and control populations showed no difference in basal and induced AHH activity of AHH inducibility. The mean AHH inducibility in patients who had lung cancer was 3.20 +/- 0.20; in patients who had laryngeal cancer 2.96 +/- 0.18, and for all controls 3.29 +/- 0.04 (no significant difference at p = 0 05). Further analysis of the distribution of AHH inducibility in the patient group compared to controls showed no suggestion of a shift toward the higher end of the range in patients who had lung and laryngeal cancer.

Adenocarcinoma↗
PubMed1978

Comparison of benzo[a]pyrene metabolism by human peripheral blood lymphocytes and monocytes.

Here we report a more sensitive high-pressure liquid chromatographic (HPLC) assay of benzo[a]pyrene (BP) metabolites elaborated by human monocytes and lymphocytes using only 10 X 10(6) cells for HPLC analysis. The major metabolites formed by both lymphocytes and monocytes were 3-hydroxy-BP, 9-hydroxy-BP and quinones. BP-dihydrodiols were also found by HPLC analysis, the major one being BP-7,8-dihydrodiol for both cell types. In addition, a peak slightly more polar than 9,10-dihydrodiol was formed by lymphocytes. The 7,8-diol peak was eliminated by the addition of 1,1,1-trichloropropene oxide to the incubation mixture. The presence of alpha-napthoflavone resulted in an overall decrease in metabolite production.

Benzopyrenes↗
PubMed1978

Study on the mutagenicity of conjugated estrogens in human, animal and bacterial systems.

Conjugated estrogens were studied for mutagenicity (and implied carcinogenicity) in two strains of S. typhimurium, two normal and three neoplastic human lymphoid cell lines (the latter from Burkitt's lymphoma patients) in cell culture and a Chinese hamster cell line in diffusion chambers implanted into mice. No significant increase in mutation rate or chromosome aberrations were noticed after exposure to conjugated estrogens.

Animals↗
PubMed1978

Aryl hydrocarbon hydroxylase in cultured lymphocytes of twins.

Measurement of aryl hydrocarbon hydroxylase (AHH) in cultured lymphocytes of 18 monozygotic and 30 dizygotic twin pairs showed that basal and induced AHH activity and AHH inducibility are heritable traits. The data are consistent with AHH inducibility being determined by a single or a very few polymorphic genes.

Aryl Hydrocarbon Hydroxylases↗
PubMed1977

Questionable relation of aryl hydrocarbon hydroxylase to lung-cancer risk.

To test whether the genetically determined trait, aryl hydrocarbon hydroxylase inducibility, affects susceptibility to lung cancer, we measured this trait in cultured lymphocytes from a normal population, patients with lung cancer and progeny of such patients. We found very low aryl hydrocarbon hydroxylase activity (19 per cent of normal) in about half the patients with lung cancer. Only part of this activity can be accounted for by reduced cell growth and by reduced protein synthesis. In an indirect assessment of inducibility, both 57 progeny and 27 matched controls had a mean inducibility of 2.95 and a similar distribution into low, intermediate and high groups (chi-square = 0.3 P = 0.9). No differences in basal or induced activity were observed. Thus, if patients with lung cancer possess altered aryl hydrocarbon hydroxylase inducibility or activity these characteristics are not transmitted to their progeny.

Adult↗
PubMed1977

Distribution of aryl hydrocarbon hydroxylase inducibility in cultured human lymphocytes.

We measured aryl hydrocarbon hydroxylase (AHH) in cultured human lymphocytes. A striking seasonal variation in AHH activity was observed with induced AHH activity levels from January through May measuring approximately 20% of the values during the remainder of the year. AHH inducibility was determined by comparing lymphocytes from the same person cultured with and without the inducer 3-methylcholanthrene. If measurements are limited to the summer and fall seasons when AHH activity is high, AHH inducibility is reproducible for most persons with repeat determinations on the same person averaging 11% from the mean. The values of AHH inducibility in 53 persons ranged from 0.9 to 5.0, but the distribution of values did not fall into three distinct, nonoverlapping classes as reported by others. We were not able to determine the distribution of AHH inducibility in lung cancer patients since lymphocytes from less than half of the patients tested could be successfully cultured.

Aryl Hydrocarbon Hydroxylases↗
PubMedDate not supplied

Theophylline disposition in residents living near a chemical waste site.

The pharmacokinetics of theophylline were compared in 11 residents living near a chemical waste site (Love Canal) and 25 control subjects from Western New York. Love Canal residents had documented chronic exposure to a variety of organic and halogenated compounds. Only young adults with no overt diseases were examined. Theophylline plasma clearances were similar in the two groups, although the enzyme inductive effects of tobacco smoking were further confirmed. The lack of environmental effect on theophylline clearance indicates that no chronic net change in one pathway of microsomal P-448 oxidation occurred. The possibility of acute changes related to seasonal chemical exposure and mixed inductive/repressive effects from the myriad types of chemicals may confound the data.

Adult↗
PubMedDate not supplied

Atherosclerosis susceptibility differences among progenitors of recombinant inbred strains of mice.

Female mice of 16 inbred mouse strains were fed an atherogenic diet for 14 weeks and were then evaluated for atherosclerotic lesions in the aorta. Strains C57BL/6, C57BR/cd, C57L, and SM were very susceptible to atherosclerosis, with lesion area/aortic cross-sections in the range of 4500 to 8000 microns 2. Strains C58 and SWR were intermediate in susceptibility, with lesion area/sections in the range of 1670 to 1690 microns 2. Strains 129, AKR, DBA/2, and BALB/c had only small lesions in the range of 20 to 350 microns 2/section; strains C3H, NZB, CBA, HRS, SJL, and A had no lesions after 14 weeks. Lesion formation in five strains was compared at several time points. Strain C57BL/6 mice developed lesions by 7 weeks, and these continued to grow until all mice had large atheromatous plaques in the aorta and coronary arteries. Strains AKR and DBA/2 also had fatty streak lesions as early as 7 or 8 weeks, but these lesions had not progressed in size by 14 weeks. Strains BALB/c and C3H, which were both resistant to lesion formation at 14 weeks, diverged from each other as time progressed. By 1 year, BALB/c mice had large lesions, but C3H mice had none. Most of the inbred strains chosen for evaluation are the progenitors of recombinant inbred sets of strains, a genetic tool that greatly facilitates the analysis of strain differences. This survey indicates seven additional recombinant inbred sets of strains whose progenitors differ in atherosclerosis susceptibility: BXD, AKXL, SWXJ, NX8, 129XB, NXSM, and B6NXAKRN. An analysis of these recombinant inbred strains may reveal additional mouse genes affecting atherosclerosis susceptibility.

Animals↗
PubMedDate not supplied

Analysis of atherosclerosis susceptibility in mice with genetic defects in platelet function.

To determine whether platelets contribute to the development of atherosclerosis, we compared the severity of atherosclerosis in susceptible C57BL/6 mice carrying either a normal or a variant phenotype for platelet function. Five genetically distinct mutants with increased bleeding times and abnormal dense granules were used: maroon (ru-2mr), light ear (le), ruby eye (ru), beige (bg1), and pale ear (ep). After a 14-week consumption of an atherogenic diet, three mutants had significantly less disease involvement than the control: light ear, maroon, and ruby eye. In contrast, pale ear ahd lesions similar to control animals. After 48 weeks, the two mutants with the least degree of atherosclerosis at 14 weeks, light ear and ruby eye, showed greater than 50% survival. In contrast, no animals from the beige, pale ear, or the normal C57BL/6 strains survived. To determine whether a specific biochemical component of platelet function is related to atherosclerosis, we measured serotonin found in dense granules. Serotonin showed no correlation with each mutant's atherosclerosis susceptibility. These results indicate that some particular component of platelet function affects atherosclerosis. That component is intact in pale ear, moderately affected in beige and maroon, and severely affected in light ear and ruby eye. The identity of that component remains an interesting question whose answer may provide further insight into the atherosclerotic disease process.

Animals↗
PubMedDate not supplied

Additional evidence that the K-ras protooncogene is a candidate for the major mouse pulmonary adenoma susceptibility (Pas-1) gene.

A locus for mouse pulmonary adenoma susceptibility, Pas-1, has been mapped on distal chromosome 6, where the K-ras gene is located. Allele-specific activation and expression of the K-ras allele from the susceptible parent has been observed in lung tumors from F1 hybrid mice. We report here genetic mapping of lung tumor susceptibility genes in urethane-treated A x B and B x A recombinant inbred (RI) mice using microsatellite markers to seek further evidence for the K-ras gene as candidate for Pas-1. The K-ras genotype differs between the A/J and C57BL/6J progenitors of the RI strains, and distal chromosome 6 contained a major lung tumor susceptibility determinant in the RI mice. Additional evidence that Pas-1 is K-ras involved linkage analysis of (A/JOLaHsd x BALB/ cOLaHsd) F2 intercross mice whose parents shared the same K-ras genotype. In contrast to the results with the A x B and B x A RI strains, no distal chromosome 6 site was significantly associated with tumor development in these F2 mice. In addition to this major locus, linkage analysis of the RI mice revealed additional quantitative trait loci for susceptibility on chromosomes 10, 17, and 19. These loci may serve as modifiers of Pas-1. The relationship between the K-ras genotype and the frequency of K-ras mutations in urethane-induced lung tumors from the RI mice was also explored. All 18 tumor DNAs from RI mice with high susceptibility contained an AT-->TA transversion at the second base of K-ras codon 61. This was also true for DNAs from 27 of 27 (100%) tumors in mice with high intermediate susceptibility. In RI strains with a low intermediate susceptibility, the DNA from 39 of 47 (83%) tumors contained an AT-->TA transversion at codon 61, and only 13 of 21 (62%) tumors had this mutation in the most resistant group. This reflects a positive correlation between the frequency of K-ras mutations in lung tumors of A x B or B x A RI strains and their susceptibility to lung carcinogenesis. Since K-ras appears to be Pas-1, these results suggest that some RI mice that have the resistant K-ras or Pas-1 allele undergo tumor development by a K-ras-independent route.

Adenoma↗