PMID- 20069279
OWN - NLM
STAT- MEDLINE
DCOM- 20110615
LR  - 20181201
IS  - 1432-0738 (Electronic)
IS  - 0340-5761 (Linking)
VI  - 84
IP  - 3
DP  - 2010 Mar
TI  - A Mechanism for the induction of renal tumours in male Fischer 344 rats by 
      short-chain chlorinated paraffins.
PG  - 233-43
LID - 10.1007/s00204-009-0489-9 [doi]
AB  - Short-chain chlorinated paraffins (SCCPs) cause kidney tumours in male rats, but 
      not in female rats or mice of either sex. Male rat-specific tumours also occur in 
      rats dosed with a range of compounds including 1,4- dichlorobenzene (DCB) and 
      d-limonene (DL). These compounds bind to a male rat-specific hepatic protein, 
      alpha-2-urinary globulin (alpha2u), and form degradationresistant complexes in the 
      kidney. The resulting accumulation of alpha2u causes cell death and sustained 
      regenerative cell proliferation, which in turn leads to the formation of renal 
      tumours. To investigate whether the SCCP, Chlorowax 500C (C500C), causes tumours 
      via the accumulation of alpha2u male rats were orally dosed with either C500C (625 
      mg/kg of body weight), DCB (300 mg/kg of body weight), or DL (150 mg/kg of body 
      weight) for 28 consecutive days. An increase in renal alpha2u and cell proliferation 
      was observed in DCB- and DL-treated rats but not in C500C-treated rats. C500C 
      caused peroxisome proliferation and a down-regulation of alpha2u synthesis in male 
      rat liver. This down-regulation occurred at the transcriptional level. Since less 
      alpha2u was produced in C500C-treated rats, there was less available for accumulation 
      in the kidney hence a typical alpha2u nephropathy did not appear. However, the 
      administration of a radiolabelled SCCP, [14C]polychlorotridecane (PCTD), to male 
      rats demonstrated its binding to renal alpha2u. Thus, it is possible that SCCPs bind 
      to alpha2u and cause a slow accumulation of the protein in the kidney followed by 
      delayed onset of alpha2u nephropathy. As a consequence of these findings in the 
      current experiments, while evidence exists implicating alpha2u-globulin in the 
      molecular mechanism of action of the C500C, the classic profile of a alpha2u-globulin 
      nephropathy seen with other chemicals such as DCB and DL was not reproduced 
      during this experimental protocol.
FAU - Warnasuriya, Gayathri D
AU  - Warnasuriya GD
AD  - Biomedical Research Centre, Ninewells Hospital and Medical School, University of 
      Dundee, Dundee DD1 5JJ, UK.
FAU - Elcombe, Barbara M
AU  - Elcombe BM
FAU - Foster, John R
AU  - Foster JR
FAU - Elcombe, Clifford R
AU  - Elcombe CR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Arch Toxicol
JT  - Archives of toxicology
JID - 0417615
RN  - 0 (Alpha-Globulins)
RN  - 0 (Carcinogens)
RN  - 0 (Chlorobenzenes)
RN  - 0 (Cyclohexenes)
RN  - 0 (Hydrocarbons, Chlorinated)
RN  - 0 (Terpenes)
RN  - 0 (alpha 2u globulin)
RN  - 56509-64-9 (chlorowax 500C)
RN  - 9MC3I34447 (Limonene)
RN  - D149TYB5MK (4-dichlorobenzene)
SB  - IM
MH  - Alpha-Globulins/genetics/*metabolism
MH  - Animals
MH  - Carcinogens/*metabolism/toxicity
MH  - Cell Proliferation/drug effects
MH  - Chlorobenzenes/metabolism/toxicity
MH  - Cyclohexenes/metabolism/toxicity
MH  - Disease Models, Animal
MH  - Down-Regulation/drug effects
MH  - Female
MH  - Hydrocarbons, Chlorinated/*metabolism/toxicity
MH  - Kidney/drug effects/metabolism
MH  - Kidney Neoplasms/chemically induced/*metabolism/pathology
MH  - Limonene
MH  - Liver/drug effects/metabolism
MH  - Male
MH  - Peroxisomes/drug effects
MH  - Protein Binding
MH  - Rats
MH  - Rats, Inbred F344
MH  - Terpenes/metabolism/toxicity
MH  - Transcription, Genetic/drug effects
EDAT- 2010/01/14 06:00
MHDA- 2011/06/16 06:00
CRDT- 2010/01/14 06:00
PHST- 2009/11/06 00:00 [received]
PHST- 2009/11/10 00:00 [accepted]
PHST- 2010/01/14 06:00 [entrez]
PHST- 2010/01/14 06:00 [pubmed]
PHST- 2011/06/16 06:00 [medline]
AID - 10.1007/s00204-009-0489-9 [doi]
PST - ppublish
SO  - Arch Toxicol. 2010 Mar;84(3):233-43. doi: 10.1007/s00204-009-0489-9.