Sensitivities of peripheral lymphocytes from healthy humans to induction of sister chromatid exchanges by chemicals.

The spontaneous sister chromatid exchanges (SCEs) and SCEs induced by 50 microM methyl methanesulfonate, 1 microM 4-nitroquinoline 1-oxide, and 5 microM 3-amino-1-methyl-5H-pyrido[4,3-b]indole were examined in phytohemagglutinin-activated peripheral lymphocytes from 53 healthy adult donors. The means of the mean spontaneous SCEs and SCEs induced by methyl methanesulfonate, 4-nitroquinoline 1-oxide, and 3-amino-1-methyl-5H-pyrido[4,3-b]indole in cells of these donors had coefficients of variability of 12, 14, 24, and 28%, respectively. Thus, it was possible to estimate the SCE-inducing activities of chemicals in peripheral lymphocytes from a population of healthy humans under the defined experimental conditions. These facts provide one of the useful parameters for evaluating the genotoxicities of chemicals to human beings, a genetically heterogeneous species. Cells from two of the donors were considerably more sensitive to particular chemicals than were those from other donors, consistently giving higher numbers of induced SCEs in two repeat examinations.

Epstein-Barr virus-transformed human lymphoblastoid cells for study of sister chromatid exchange and their evaluation as a test system.

Epstein-Barr virus-transformed human lymphoblastoid cell lines are suitable for detection of sister chromatid exchange (SCE) induced by mutagens-carcinogens because they have shown a stable chromosome number and stable frequency of spontaneous SCE for more than two years in culture. Their spontaneous and induced SCE frequencies were practically the same as those of phytohemagglutinin-stimulated lymphocytes from the same blood donors. The SCE responses of one established cell line, NL3, to 13 typical mutagens and five nonmutagens were examined. This cell line responded to all the mutagens tested but not to the nonmutagens. The SCE-inducing activities of these chemicals were well correlated with their mutagenic activities assayed with the Salmonella system by Ames' and Sugimura's groups, although there were a few but significant deviations.

Novel responses of peripheral lymphocytes of cancer patients to chemical induction of sister chromatid exchanges.

Sensitivities to sister chromatid exchange (SCE) induction by chemicals of peripheral lymphocytes from 26 cancer patients were estimated under conditions identical to those for healthy humans which had been reported (Cancer Res., 43: 439-442, 1983). The sensitive individual was defined as one whose cells give a mean induced SCE frequency more than 2 standard deviation units above the population mean of induced SCEs in cells from the healthy humans. When cells were treated with 3-amino-1-methyl-5H-pyrido[4, 3-b]indole in the presence of rat liver S9 mix, 8 in 10 stomach cancer patients, 4 in 4 colon cancer patients, 3 in 9 lung cancer patients, 0 in 3 patients bearing other cancers, and 0 in 9 non-cancerous individuals were sensitive. The corresponding frequency of individuals in the healthy population, reported previously, was 1 in 33 persons. Thus, the frequency of sensitive individuals in the combined group of stomach and colon cancer patients was very significantly higher than were frequencies in control groups. Three in 10 patients with stomach cancer and 4 in 16 patients with other cancers were sensitive to induction of SCE by methyl methanesulfonate. Six in these 7 methyl methanesulfonate-sensitive patients were also 3-amino-1-methyl-5H-pyrido[4,3-b]indole sensitive. The frequency of methyl methanesulfonate-sensitive individuals in the healthy populations was 2 in 50. There was no patient who was sensitive to SCE induction by 4-nitroquinoline 1-oxide. The frequency was not significantly different from the healthy population, in which 3 in 50 persons were sensitive. These results suggest that a particular cancer correlates with the sensitivity of peripheral lymphocytes to SCE induction by particular chemicals.