Renal tubular tumors and atypical hyperplasias in B6C3F1 mice exposed to lead acetate during gestation and lactation occur with minimal chronic nephropathy.
Lead is a high-priority hazardous substance in humans and a renal carcinogen in adult rodents. This study assessed the carcinogenic potential and toxicity of gestational and lactational lead exposure in (C57BL/6NCr x C3H/HeN)F1 (hereafter called B6C3F1) mice. Effects of a renal tumor promoter [barbital sodium (BB)] on lead-initiated lesions were also studied. Pregnant female C57BL/6NCr mice (10-15/group) previously bred with C3H/HeN males were given lead acetate (0, 500, 750 and 1000 ppm lead) ad libitum in their drinking water, starting on gestation day 12 and continuing to 4 weeks postpartum. Offspring were then weaned and divided into same-sex groups of 23-25 and observed for a maximum of 112 weeks. Other groups received lead and then continuous BB (500 ppm) ad libitum in their drinking water from weaning onward. In control male offspring (0 lead/0 BB), renal proliferative lesions [(RPLs); defined as atypical tubular hyperplasia or tumor] occurred rarely (1 lesion-bearing mouse/23 mice examined, 4%) and did not include tumors. RPLs increased in a dose-related fashion with lead exposure (500 lead/0 BB, 4/25, 16%; 750 lead/0 BB, 6/25, 24%; 1000 lead/0 BB, 12/25, 48%) in male offspring and were often multiple. All lead-treated groups had renal tumors, including carcinoma, but these were most common at the highest dose (1000 lead/0 BB, 5/25). Lead-induced renal tumors arose in the absence of the extensive chronic nephropathy and lead inclusion bodies typically seen with lead carcinogenesis in rodents exposed chronically as adults. Postnatal BB exposure had no effect on RPL incidence (e.g., 1000 lead/500 BB, 8/25, 32%). Lead-treated female offspring also developed RPLs, including adenoma and carcinoma, but at a much lower rate than males. Thus, short-term lead exposure during the gestational/lactational period has carcinogenic potential in the mouse kidney.
Waalkes
M P
MP
Inorganic Carcinogenesis Section, Science Applications International Corporation-Frederick, National Cancer Institute, Maryland 21702-1201, USA.
Diwan
B A
BA
Ward
J M
JM
Devor
D E
DE
Goyer
R A
RA
D000818:Animals; D001462:Barbital / Q000633:toxicity; D002273:Carcinogens / Q000633:toxicity*; D002908:Chronic Disease; D005260:Female; D005333:Fetus / Q000187:drug effects*; D006965:Hyperplasia; D007680:Kidney Neoplasms / Q000139:chemically induced*; D007684:Kidney Tubules / Q000187:drug effects* / Q000473:pathology; D007774:Lactation; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000633:toxicity*; D011247:Pregnancy
D002273:Carcinogens; D009942:Organometallic Compounds; D001462:Barbital; C008261:lead acetate