Genotoxic effects of benzyl isothiocyanate, a natural chemopreventive agent

Benzyl isothiocyanate (BITC) is contained in cruciferous plants which are p art of the human diet. Numerous reports indicate that BITC prevents chemica lly induced cancer in laboratory animals and it has been postulated that BI TC might also be chemoprotective in humans. On the other hand, evidence is accumulating that this compound is a potent genotoxin in mammalian cells by itself. To further elucidate the potential hazards of BITC, we investigate d its genotoxic effects in different ill vitro genotoxicity tests and in an imal models. In irt vitro experiments [differential DNA repair assay with E scherichia coli, micronucleus assay with human HepG2 cells and single cell gel electrophoresis (SCGE) assay with hepatocytes and gastrointestinal trac t cells] pronounced dose-dependent genotoxic effects were found at low dose levels (less than or equal to 5 mu g/ml). In contrast, substantially weake r effects were obtained in in vivo experiments with laboratory rodents: in the differential DNA repair assay with E. coli cells, only moderate genotox ic effects were seen in indicator cells recovered from various organs of mi ce after treatment with high doses (between 90 and 270 mg/kg), while in SCG E assay with rats a change in the DNA migration pattern was seen at a dose level of 220 mg/ kg body wt. These findings indicate that BITC is detoxifie d under in vivo test conditions. This assumption was supported by the resul ts of in vitro experiments which showed that the genotoxic effects of BITC are markedly reduced by bovine serum albumin and human body fluids such as saliva and gastric juice. Additional experiments carried out on the mechani stic aspects of the genotoxicity of BITC showed that this compound causes f ormation of thiobarbituric acid-reactive substances in HepG2 cells and that its DNA damaging properties are diminished by alpha-tocopherol, vitamin C, sodium benzoate and beta-carotene, indicating the possible involvement of free radicals in the genotoxicity of BITC, The doses of BITC required to ca use measurable DNA damage in laboratory rodents exceeded by far the dietary exposure levels of humans, but are similar to those which were required to inhibit chemically induced cancer in earlier animal experiments.