In this paper, we have compared mutant frequency data at the hprt locus in circulating T-lymphocytes from four large datasets obtained in the UK (Sussex), the USA (Vermont), France (Paris) and The Netherlands (Leiden). In total, data from > 500 non-exposed individuals ranging in age from newborns (cord blood samples) to > 80 years old have been included in the analysis. Based on raw data provided by the four laboratories, a model is presented for the analysis of mutant frequency estimations for population monitoring. For three of the laboratories, a considerable body of data was provided on replicate estimates of mutant frequency from single blood samples, as well as estimates from repeat blood samples obtained over a period of time from many of the individual subjects. This enabled us to analyse the sources of variation in the estimation of mutant frequency. Although some variation was apparent in the results from the four laboratories, overall the data were in general agreement. Thus, in all laboratories, cellular cloning efficiency of T-cells was generally high (> 30%), although in each laboratory considerable variation between experiments and subjects was seen. Mutant frequency per clonable T-cell was in general found to be inversely related to cloning efficiency. With the exception of a few outliers (which are to be expected), mutant frequencies at this locus were in the same range in each dataset; no effect of subject gender was found, but an overall clear age effect was apparent. When log mutant frequency was analysed vs log (age + 0.5) a consistent trend from birth to old age was seen. In contrast, the effect of the smoking habit did differ between the laboratories, there being an association of smoking with a significant increase in mutant frequency in the Sussex and Leiden datasets, but not in those from the Vermont or Paris datasets. Possible reasons for this are discussed. One of the objectives of population monitoring is an ability to detect the effect of accidental or environmental exposure to mutagens and carcinogens among exposed persons. The large body of data from non-exposed subjects we have analysed in this paper has enabled us to estimate the size of an effect that could be detected, and the number of individuals required to detect a significant effect, taking known sources of variation into account.(ABSTRACT TRUNCATED AT 400 WORDS)

Adolescent↗

PubMedDate not supplied

The basal and the mutagen-induced levels of ADP-ribosyl transferase activity are not modified in Fanconi's anemia cells.

The activity of ADP-ribosyl transferase, an enzyme thought to be involved in several basic functions of the chromatin and in DNA repair, has been investigated in normal and Fanconi's anemia (FA) cells. Fibroblasts and lymphoblasts treated with alkylating (dimethyl sulfate) or cross-linking (mitomycin C, psoralen plus UVA) agents were compared to untreated cells. The basal level of the enzymatic activity was found to be the same in normal and FA cells and the enzymatic response to treatments with DNA-damaging agents was similar in both cell types. Consequently it is unlikely that the molecular defect in FA cells is due to a decreased activity in ADP-ribosyl transferase.

Anemia, Aplastic↗

PubMedDate not supplied

Photochemotherapy using pyridopsoralens.

Aiming to decrease the acute side effects and genotoxic hazards of PUVA, pyrido (3,4-C) psoralen (PP) and 7-methyl pyrido (3,4-C) psoralen (MPP) were synthesized and studied. Their UVA maximum absorption lies at 325 and 330 nm, respectively. Their photostability is comparable to that of 8-MOP. They complex to DNA in the dark, and, in the presence of UVA, produce only monoadditions to DNA, as shown by fluorescence and DNA denaturation-renaturation studies. In diploid eukaryotic yeast they are more effective than 8-MOP for the induction of lethal effects and mitochondrial damage. Their mutagenic activity per unit dose of UVA is in the same range as that of 8-MOP. However, per viable cell they are clearly less mutagenic than 8-MOP. This difference is also observed for recombinogenic activity. No oxygen effect is observed. In mammalian cells the following ranges of effectiveness are found: inhibition of DNA synthesis in human fibroblasts: MPP greater than PP greater than 8-MOP; mutagenic activity in V79 Chinese hamster cells: MPP greater than PP greater than 8-MOP; cell transforming ability in C3H embryonic mouse cells: MPP greater than 8-MOP greater than PP as a function of UVA dose, and: 8-MOP greater than MPP greater than PP as a function of survival; induction of sister chromatic exchanges (SCE) per unit dose: MPP greater than PP greater than 8-MOP in the linear part of the induction curve, and : 8-MOP greater than PP greater than MPP at the maximum level of SCE obtained.(ABSTRACT TRUNCATED AT 250 WORDS)

5-Methoxypsoralen↗

PubMedDate not supplied

DNA repair pathways and dose responses to ionizing radiations.

Explore the source record for details and available documents.

Cell Death↗

PubMedDate not supplied

[Tumor and individual radiosensitivity. An introduction].

This text is intended to introduce the following articles, which correspond to the lectures given at the "Radiosensitivity" session of the 1998 SFRO Meeting. We first underline the somewhat disappointing results obtained so far for evaluating tumoral radiosensitivity. However, a few new tests could bring some hope in a not-too distant future. We then focus on individual radiosensitivity. We first list the syndromes or diseases associated with a known hyperradiosensitivity. We then concentrate on the radiosensitivity tests that are available in 1998, some of them being already used in a few centers in specific situations. However, the "optimal" test is still to be identified. After a brief chapter on the possible modulations of radiosensitivity, we conclude with a few recommendations to the clinician.

Causality↗