Characterization of lymphocyte stimulation by phorbol related compounds.

1. The stimulation of (3H)-thymidine incorporation by lymphocytes in response to phorbol and seven other phorbol related compounds was investigated. 2. Lymphocytes from each of a small group of individuals were treated with the test compounds over wide concentration ranges. 3. All the tested compounds, including the most active, 12-0-tetradecanoylphorbol-13-acetate, were far less effective lymphocyte mitogens than the plant lectin phytohaemagglutinin. 4. Inter-individual differences were detected in the maximum response to the phorbols but not in their stimulating potency, as estimated by the concentration producing a half maximal response. 5. The rank order of the lymphocyte stimulating potency of the tested compounds was similar to the rank order of both tumour promoting activity and irritant potency in mouse skin. 6. Lymphocyte stimulation was paralleled equally well by these two mouse skin responses.

Chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index in peripheral lymphocytes from 106 control individuals of the U.K. population.

Blood samples were taken from 106 individuals (73 males and 33 females) and examined for chromosome aberrations, mitogen-induced blastogenesis and proliferative rate index (PRI). The values obtained were investigated in relation to sex, age, smoking, alcohol consumption and X-ray exposure. In all the parameters, there was shown to be a difference between the mean values for the males and females. The incidence of chromosome aberrations was greater in females than in the males, whereas the mean values of PRI and mitogen-induced blastogenesis were lower in females than in the males. A sex difference has been reported previously in the same population, in that the females were shown to have a higher rate of sister-chromatid exchanges than the males (Anderson et al., 1986; Dewdney et al., 1986). Contraceptive pill usage was not considered to be of importance in the sex difference seen and there was shown to be no significant influence due to age, smoking or alcohol consumption on any of the parameters except that smoking reduced lymphocyte PRI. Males with previous X-ray exposure also showed a lower response to mitogen-induced blastogenesis and had a reduced PRI.

Chromosomal aberrations and sister chromatid exchanges in lymphocytes and urine mutagenicity of migraine patients: a comparison of chronic feverfew users and matched non-users.

1. Thirty migraine patients who had taken the leaves, tablets or capsules of feverfew daily for more than 11 consecutive months were compared to 30 feverfew non-user migraine patients who had been individually age- and sex-matched. 2. The frequency of chromosomal aberrations and sister chromatid exchanges (SCE) were determined from lymphocyte cultures established from blood samples taken over a period of several months. Matched pairs were sampled on the same date for two-thirds of the cases, and the greatest difference in sampling time of the remainder was 20 days. Also, the mutagenicity of urine samples from 10 feverfew user migraine patients was compared to that from 10 matched non-user migraine patients using the Ames Salmonella mutagenicity test system. Paired samples were given on the same date. 3. The mean frequency of chromosomal aberrations in the feverfew user group was lower than that in the non-user group both in terms of cells with breaks (2.13% vs 2.76%) and in terms of cells with all aberrations (4.34% vs 5.11%). However, this difference was small and not significant. 4. The mean frequency of SCE in the feverfew exposed group was lower than that in the control group (8.78 vs 8.80 SCE/cell), but, this difference was not significant as determined by factorial analysis of variance (P = 0.897). There was a highly significant variance between the frequencies of SCE in the matched pairs of migraine patients but this was not related to age, sex or feverfew exposure.(ABSTRACT TRUNCATED AT 250 WORDS)

Variation in sister-chromatid exchange among 106 members of the general U.K. population.

SCE scores of lymphocytes from 106 people revealed that the majority of background variation in SCE was between cells within individuals. Highly significant differences existed between individuals. Lesser, but still highly significant differences also existed between replicate cultures. Inter-individual variation was contributed to by each person's sex and their smoking habits. SCE frequency was not influenced by any of the other factors considered, age, drinking habits and diagnostic X-ray exposure of persons or lymphocyte number and proliferation rate in cultures.

Sister chromatid exchange (SCE) analysis in 106 control individuals.

PIP: This study was aimed at obtaining baseline data on the degree of variability of sister chromatid exchange (SCE) values in 106 individuals. There were highly significant differences between individuals and between replicate serum cultures within individuals in SCE frequencies. Females had significantly higher SCE frequencies than males, and cigarette smoking significantly increased such values after correction for sex. On the basis of this study, the following recommendations are proposed for future studies monitoring SCE frequencies in control and exposed populations: 1) subjects should be matched by sex and smoking status; 2) 50 cells per individual with 25 from 2 replicate cultures is a suitable sample size; 3) either the original data or the means should be transformed to logarithms for analysis; 4) the dispersion test should be carried out and the H statistic (variance/mean) should be reported; 5) differences between control and exposed groups can be analyzed either by analysis of variance or nonparametric methods; 6) the sample size should be based on considerations of the significance level required and interindividual variability; 7) concurrent controls are advisable when using statistics based on background incidences; and 8) quality control methods should be applied to routine collection of background control data.^ieng

A mutagenesis-enhancing activity of 12-O-tetradecanoylphorbol 13-acetate detected in Chinese hamster ovary cells.

Tumour-promoting agents may bring about the completion of multi-step carcinogenesis by acting as enhancers of mutagenesis, recombinogens or clastogens. We report here that the classical mouse skin tumour promoter TPA, although non-mutagenic per se, can enhance the induction of OuaR CHO-K1 cell mutants by MNNG approximately 2-fold. This observation was made at a concentration approaching the compounds aqueous solubility limit which was non-cytotoxic. Mutagenesis enhancement was dependent on TPA being present throughout mutation expression and mutant selection. It was not accompanied by any modification of cell sensitivity to mutagen killing. In the same treatment protocol TPA did not enhance either EMS- or UV-induced mutagenesis. TPA exposure over 2 rounds of cell replication failed to produce an increase in the frequency of SCE in control or mutagen-treated CHO-K1 cultures. Likewise TPA exposure over 1 round of cell replication failed to produce an increase in the frequency of chromosomal aberrations. Apparently TPA is not a recombinogen or clastogen but in the right exposure regime is capable of acting to enhance mutagenesis by certain genotoxic agents, an action which may contribute to tumour promotion.