This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Waalkes, M. P. Articles by Goyer, R. A. Search for Related Content PubMed PubMed Citation Articles by Waalkes, M. P. Articles by Goyer, R. A.

Renal Tubular Tumors and Atypical Hyperplasias in B6C3F₁ Mice Exposed to Lead Acetate during Gestation and Lactation Occur with Minimal Chronic Nephropathy¹

Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis [M. P. W.], Biological Carcinogenesis and Development Program, Science Applications International Corporation-Frederick [B. A. D.], and Veterinary and Tumor Pathology Section, Office of Laboratory Animal Science [J. M. W., D. E. D.], National Cancer Institute, Frederick Cancer Research & Development Center, Frederick, Maryland 21702-1201, and Department of Pathology, University of Western Ontario, London, Ontario, Canada [R. A. G.]

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.

¹ Presented in part at the 1995 Society of Toxicology Annual Meeting, March 5–9, 1995, Baltimore, MD. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the U. S. government.

² To whom requests for reprints should be addressed, at Inorganic Carcinogenesis Section, Laboratory of Comparative Carcinogenesis, National Cancer Institute, Frederick Cancer Research & Development Center, Building 538, Room 205E, Frederick, MD 21702-1201.

Received 6/12/95. Accepted 9/19/95.

This article has been cited by other articles:

				N. Healey Lead toxicity, vulnerable subpopulations and emergency preparedness Radiat Prot Dosimetry, June 1, 2009; 134(3-4): 143 - 151. [Abstract] [Full Text] [PDF]

				M. P. Waalkes, J. Liu, R. A. Goyer, and B. A. Diwan Metallothionein-I/II Double Knockout Mice Are Hypersensitive to Lead-Induced Kidney Carcinogenesis: Role of Inclusion Body Formation Cancer Res., November 1, 2004; 64(21): 7766 - 7772. [Abstract] [Full Text] [PDF]

				M. P. Waalkes, J. Liu, H. Chen, Y. Xie, W. E. Achanzar, Y.-S. Zhou, M.-L. Cheng, and B. A. Diwan Estrogen Signaling in Livers of Male Mice With Hepatocellular Carcinoma Induced by Exposure to Arsenic In Utero J Natl Cancer Inst, March 17, 2004; 96(6): 466 - 474. [Abstract] [Full Text] [PDF]

				M. P. Waalkes, J. M. Ward, and B. A. Diwan Induction of tumors of the liver, lung, ovary and adrenal in adult mice after brief maternal gestational exposure to inorganic arsenic: promotional effects of postnatal phorbol ester exposure on hepatic and pulmonary, but not dermal cancers Carcinogenesis, January 1, 2004; 25(1): 133 - 141. [Abstract] [Full Text] [PDF]

				W. Qu, B. A. Diwan, J. Liu, R. A. Goyer, T. Dawson, J. L. Horton, M. G. Cherian, and M. P. Waalkes The Metallothionein-Null Phenotype Is Associated with Heightened Sensitivity to Lead Toxicity and an Inability to Form Inclusion Bodies Am. J. Pathol., March 1, 2002; 160(3): 1047 - 1056. [Abstract] [Full Text] [PDF]

				M. Valverde, T. I. Fortoul, F. Diaz-Barriga, J. Mejia, and E. R. del Castillo Genotoxicity induced in CD-1 mice by inhaled lead: differential organ response Mutagenesis, January 1, 2002; 17(1): 55 - 61. [Abstract] [Full Text] [PDF]

				J. M. Rice and J. D. Wilbourn Tumors of the Nervous System in Carcinogenic Hazard Identification Toxicol Pathol, January 1, 2000; 28(1): 202 - 214. [Abstract] [PDF]