Six chemicals, known to induce kidney tumors in rats, were examined for their ability to induce DNA fragmentation and
formation of micronuclei in primary cultures of rat and human kidney cells, and in the kidney of intact rats. Significant dosedependent
increases in the frequency of DNA single-strand breaks and alkali-labile sites, as measured by the Comet assay, and in
micronuclei frequency, were obtained in primary kidney cells from both male rats and humans of both genders with the following
subtoxic concentrations of five of the six test compounds: bromodichlorometane (BDCM) from 0.5 to 4 mM, captafol (CF) from
0.5 to 2M, nitrobenzene (NB) from 0.062 to 0.5 mM, ochratoxin A (OTA) from 0.015 to 1.215M, and trichloroethylene
(TCE) from 1 to 4 mM. Benzofuran (BF), consistent with its carcinogenic activity for the kidney of female, but not of male
rats, at concentrations from 0.125 to 0.5 mM gave positive responses in cells from females but did not induce DNA damage and
increased the frequency of micronuclei in cells from males to a lower extent; in contrast, it was active in cells from humans
of both genders. DNA-damaging and micronuclei-inducing potencies were similar in the two species. In agreement with these
findings, statistically significant increases in the average frequency of both DNA breaks and micronucleated cells were obtained
in the kidney of rats, given p.o. a single dose (1/2 LD50) of the six compounds, BF in this assay being more genotoxic in female
than in male rats. Taken as a whole, these findings give further evidence that kidney carcinogens may be identified by short-term
genotoxicity assays, using as target kidney cells, and show that the six chemicals tested produce, in primary cultures of kidney
cells from human donors, effects similar to those observed in rats.