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Genotoxicity tests were performed by several laboratories with the drug fructus sennae, senna extract, sennosides, rhein and aloe-emodin. The drug fructus sennae, the sennosides and rhein did not increase mutation frequencies in the following test systems: bacterial systems (Salmonella reverse mutation test and/or Escherichia coli forward mutation test); mammalian cell cultures [hypoxanthine guanine phosphoribosyl transfer-ase (HGPRT) test; mouse lymphoma test; chromosome aberration test with Chinese hamster ovary cells]; bone marrow (micronucleus test; chromosome aberration test); melanoblast cells (mouse spot test) of rodents. With aloe-emodin mutagenic effects were observed only in vitro in the chromosome aberration test with CHO cells and in the Salmonella reverse mutation test (frameshift mutations in strains TA 1537, TA 1538 and TA 98). In the in vitro gene mutation test with V79 cells (HGPRT test) no mutagenic potential of aloe-emodin was observed. In in vivo studies [micronucleus test with bone marrow cells of NMRI mice, chromosome aberration test with bone marrow cells of Wistar rats, mouse spot test (crossing DBA/2J × NMRI) no indication for a mutagenic activity of aloe-emodin was found. The relevance of the absence of a mutagenic potential in in vivo test systems was strengthened by the fact that aloe-emodin could be found in the blood serum after oral administration. Additional information on the interaction of aloe-emodin with DNA was obtained from an ex vivo unscheduled DNA synthesis test performed with hepatocytes of male Wistar rats: aloe-emodin did not induce unscheduled DNA synthesis as expression of DNA damage. The extract of senna induced gene mutations in bacteria (frame shift mutations in TA 1537 and TA 98), but a negative result was obtained in the gene mutation test with V79 cells (HGPRT test). In the chromosome aberration test with CHO cells the senna extract induced structural chromosomal aberrations. The results demonstrate that an extract of senna and aloe-emodin were genotoxic when tested with some in vitro test systems. Under in vivo conditions so far no genotoxic effect was found. The drug fructus sennae, the sennosides and rhein were negative under in vitro as well as under in vivo conditions.

Chromosome aberrations and sister chromatid exchanges (SCEs) were evaluated in 27 workers with current 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) blood lipid concentrations exceeding 40 parts per trillion (ppt) and in 28 unexposed referents of similar age. No statistical differences were found between the two groups in the percentages of gaps, chromatid or chromosome exchanges, chromatid or chromosome breaks/fragments/deletions, multiple aberrations, or the overall percentage of aberrations including gaps (1.33% in the exposed group vs 1.75% in the referent group) or excluding gaps (0.54% in each group). There was an increased rate of SCEs per cell (P = 0.051) and a higher percentage of cells with more than 10 SCEs (P = 0.064) in the exposed group; however, these associations were no longer significant when smoking status was included as covariate. Additionally, neither current nor back-calculated TCDD concentration was a significant predictor of these parameters based on multiple linear and rank regression analyses.

The number of SCE was compared in the normal and trisomic cell lines of a trisomy 21 mosaic case. It was found that in the trisomic cells the SCE‐frequency was twice as high as in the normal cells. The mitoses with high numbers of SCE (above 10) were increased 4–5 fold. Differential chromatid staining also allowed us to determine the mitotic cycle of the mitoses. The percentage of mitoses from the fourth or a later mitotic cycle was significantly higher in the trisomic cell line than in the normal one. From this result, it can be concluded that the cell cycle time was distinctly shortened in the cells with trisomy 21.

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