Cell proliferation induced in the kidneys and livers of rats and mice by short term exposure to the carcinogen p-dichlorobenzene.
Cell proliferation in the kidneys and livers of rats and mice exposed short-term to p-dichlorobenzene (p-DCB) was evaluated by immunohistochemical measurement of bromodeoxyuridine (BrdU) incorporation into nuclei of DNA-synthesizing cells. p-DCB was given by gavage at two doses up to 600 mg/kg body weight for 4 days. The cumulative fraction of proliferating cells was increased in the proximal tubule epithelial cells of male rats at the high dose, but not at the low dose nor in females at either dose using gamma-glutamyl transferase reaction to identify tubular cells. Also, no increase in cell proliferation was found in mouse kidneys. The fractions of proliferating cells in the livers of rats and mice of both sexes were also increased. The increased cell proliferation in only male rat kidney and in the livers of mice of both sexes correlates with the reported carcinogenic effects of p-DCB in those tissues. However, the finding that p-DCB also induced cell proliferation in the livers of rats of both sexes, which were not a site of p-DCB-induced tumors in bioassays, and in female mice at the low dose, which was not affected by an increase in tumors, reveals a lack of concordance and indicates that acute induction of cell proliferation is not sufficient to lead to carcinogenesis.
Umemura
T
T
Division of Toxicology, National Institute of Health Sciences, Tokyo, Japan.
Tokumo
K
K
Williams
G M
GM
D000818:Animals; D001973:Bromodeoxyuridine / Q000378:metabolism; D002273:Carcinogens / Q000633:toxicity*; D002455:Cell Division / Q000187:drug effects; D002722:Chlorobenzenes / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects*; D007680:Kidney Neoplasms / Q000139:chemically induced; D007687:Kidney Tubules, Proximal / Q000166:cytology / Q000187:drug effects / Q000201:enzymology; D008099:Liver / Q000033:anatomy & histology / Q000166:cytology / Q000187:drug effects*; D008113:Liver Neoplasms / Q000139:chemically induced; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011916:Rats, Inbred F344; D013997:Time Factors; D005723:gamma-Glutamyltransferase / Q000032:analysis
D002273:Carcinogens; D002722:Chlorobenzenes; D005723:gamma-Glutamyltransferase; D001973:Bromodeoxyuridine; C031294:chlorobenzene