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Biomedical subjects

R R Schreck

Publications and source records attributed to R R Schreck.

33 records · Page 2Linked to original sources
PubMed1980

Comparison of benzo(a)pyrene metabolism and sister chromatid exchange induction in mice.

Genetic differences in the inducible arylhydrocarbon hydroxylase (EC 1.14.14.2) (AHH) system, which is involved in the multi-step metabolism of hydrocarbons, are known to exist in both humans and mice. However, the predictive value of AHH activity in human or murine tissues, assayed as benzo(a)pyrene hydroxylation, as an index of individual susceptibility to mutagens and carcinogens, remains unclear because of apparent inconsistencies between results obtained from different in vitro and in vivo systems. This situation may in part reflect the complexity of the pathways involved in drug metabolism, which combine both activation and detoxification. To determine the relationship of metabolic potential to an easily quantified, short-term in vivo end point of genetic damage, we compared the ability of AHH inducible and uninducible mice to metabolize a procarcinogen, benzo(a)pyrene (BP), with the in vivo induction by BP of sister chromatid exchanges (SCEs). SCE induction has been shown to correlate with mutagenesis. We report here that although BP did cause an increase in SCEs in test animals, the extent of this increase did not differ between the inducible C57BL/6 mice and the uninducible DBA/2 mice. Moreover, prior exposure to an AHH inducer, 3-methyl-cholanthrene (3-MC), did not increase the number of BP-induced SCEs in C57BL/6 mice. This lack of correlation between benzo(a)pyrene hydroxylase (BP-OH) inducibility and SCE response reinforces the idea that other metabolic steps, such as detoxification or DNA repair, may influence the overall genetic impact of a drug.

Animals↗
PubMed1979

In vivo induction of sister-chromatid exchanges in liver and marrow cells by drugs requiring metabolic activation.

A highly sensitive method for the detection of in vivo induction of sister-chromatid exchange (SCE) has been developed in mice subjected to partial hepatectomy. SCE induction by either acetylaminofluorene (AAF) or cyclophosphamide, drugs requiring metabolic activation, is significantly greater in both regenerating liver and bone-marrow cells of partial hepatectomized animals than in marrow cells of unhepatectomized mice. These experiments have confirmed the ability of AAF, a well known mutagen-carcinogen, to induce SCE formation, even though the cytogenic effects of this drug on non-hepatectomized mice is very small. The in vivo system described has demonstrated the influence of the liver on drug-induced damage to extra-hepatic tissues. The procedures developed should facilitate the detection of drug-induced cytogenic damage and permit the comparison of inter-tissue differences in SCE induction with tissue-specific differences in drug-activation pathways.

2-Acetylaminofluorene↗
PubMed1977

Preferential derivation of abnormal human G-group-like chromosomes from chromosome 15.

The marked binding of antibodies specific for 5-methylcytidine to the short arm of chromosome 15 distinguishes this chromosome from the other human acrocentrics. This method has been used to study over 60 individuals including 12 who did not have Down's syndrome, but who did have an extra G-group sized acrocentric chromosome. In six cases the extra chromosome did not show intensive binding of anti-5-methylcytidine. In the other six cases, the extra chromosome contained a 5-methylcytidine rich band at each end indicating that both ends were derived from chromosome 15 and contained centromeric heterochromatin normally present on the short arm of chromosome 15. The duplication of short arm material in the abnormal chromosomes was confirmed in all cases by quinacrine staining, nucleolar organizer (Ag-AS) staining or C-banding. In three cases, the abnormal chromosome appeared to arise from two different chromosomes 15. Several possible mechanisms for the production of the abnormal chromosome are discussed. The individuals with this abnormal chromosome all showed some degree of mental retardation, but few common physical findings.

Adult↗
PubMed1975

Chromosome markers in Mus musculus: differences in C-banding between the subspecies M.m. musculus and M.m. molossinus.

Quinacrine (Q-band) and centromeric heterochromatin (C-band) patterns of metaphase chromosomes of two subspecies of Mus musculus were compared. M.m. musculus (the laboratory mouse) and M.m. molossinus (a subspecies from Southeast Asia) had similar Q-band patterns along the length of the chromosomes, but differences were observed in the centromeric region of some chromosomes. The two subspecies had very different distributions of C-band material. Antibodies to 5-methyleytosine were bound to regions of the chromosome corresponding to the C-bands in each animal. These findings support the idea that satellite DNA, which is concentrated in the C-band region, changes more quickly than bulk DNA. The interfertility of these two subspecies permits the development of a musculus strain carrying normal marker chromosomes for genetic studies.

Animals↗
PubMed1973

Chromosome structure as revealed by a combined chemical and immunochemical procedure.

Human metaphase chromosomes were photooxidized in the presence of methylene blue, a process that destroys guanine residues in DNA. Indirect immunofluorescence showed that such chromosomes reacted with a cytosine-specific antibody revealing a consistent fluorescent banding pattern by which each chromosome could be identified. The observed fluorescent patterns were the reverse of those produced in formamide-denatured chromosomes treated with an antibody specific for adenine and of the patterns obtained with quinacrine and with Giemsa staining by the G-banding techniques. The patterns were identical to Giemsa R-banding patterns. The chromosome banding patterns, therefore, appeared to reflect DNA base composition, indicating the feasibility of a combined chemical-immunochemical investigation of the chemical organization of chromosomes.

Antibodies, Antinuclear↗