PMID- 11071396
OWN - NLM
STAT- MEDLINE
DCOM- 20010215
LR  - 20191104
IS  - 0148-0545 (Print)
IS  - 0148-0545 (Linking)
VI  - 23
IP  - 4
DP  - 2000 Nov
TI  - Role of prolactin in chloro-S-triazine rat mammary tumorigenesis.
PG  - 575-601
AB  - Chloro-S-triazine herbicides [cyanazine (CZ), atrazine (AZ), simazine (SZ)] 
      increase mammary tumors in Crl:CD BR rats but not in F-344 rats or in mice. A 
      nongenotoxic mechanism was investigated since the chloro-S-triazines are negative 
      in short-term tests for genotoxicity. An in vivo battery was used to assess the 
      chloro-S-triazines for estrogenic activity or for their ability to increase 
      prolactin (PRL) levels, both of which play important roles in enhancing mammary 
      gland tumorigenesis in rodents. Ovariectomized (OVX) female rats were treated 
      with AZ, CZ, SZ, or three CZ metabolites for 4 days via intraperitoneal 
      injection. The pattern of responses between the chloro-S-triazines and four 
      controls (estradiol, estriol, haloperidol, reserpine) was compared. For the 6 
      end-points examined, the responses from rats treated with AZ, CZ, SZ, and the 
      metabolites of CZ most closely matched the responses from the reserpine-treated 
      rats (a PRL rather than estrogenic mechanism). In addition, AZ, CZ, and SZ were 
      tested in several other in vitro models (estrogen/biogenic amine receptor 
      competition assays and a yeast-expressed human estrogen receptor transcription 
      assay) as well as an in vivo 24 h time-course experiment to characterize the 
      CZ-induced increases in PRL levels. AZ, CZ, and SZ are not estrogen receptor (ER) 
      activating compounds based on yeast transactivation and receptor competition 
      data. CZ and AZ demonstrated marginal competition (at mM levels) to the D and 
      alpha2 adrenergic receptors. Ligands to the D2 receptor, but not the alpha2 
      adrenergic receptor, are known to induce mammary tumors. CZ was also found to 
      produce elevated PRL levels in a time-course similar to that seen with reserpine 
      and haloperidol. Overall, the pattern of responses obtained with the 
      chloro-S-triazines most closely matched the responses observed for reserpine. 
      Taken together, these data suggest chloro-S-triazine-induced mammary tumors in 
      rats are mediated through a PRL mechanism, which is thought to be of low 
      relevance to humans.
FAU - O'Connor, J C
AU  - O'Connor JC
AD  - DuPont Haskell Laboratory for Toxicology and Industrial Medicine, Newark, DE 
      19714, USA. john.c.oconnor@usa.dupont.com
FAU - Plowchalk, D R
AU  - Plowchalk DR
FAU - Van Pelt, C S
AU  - Van Pelt CS
FAU - Davis, L G
AU  - Davis LG
FAU - Cook, J C
AU  - Cook JC
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Drug Chem Toxicol
JT  - Drug and chemical toxicology
JID - 7801723
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Dopamine Antagonists)
RN  - 0 (Herbicides)
RN  - 0 (Receptors, Estrogen)
RN  - 0 (Triazines)
RN  - 4TI98Z838E (Estradiol)
RN  - 8B1QWR724A (Reserpine)
RN  - 9002-62-4 (Prolactin)
RN  - FB33469R8E (Estriol)
RN  - J6292F8L3D (Haloperidol)
RN  - QJA9M5H4IM (Atrazine)
RN  - SG0C34SMY3 (Simazine)
RN  - W34C4P18WD (cyanazine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Animals
MH  - Atrazine/metabolism/*toxicity
MH  - Biological Assay
MH  - Body Weight/drug effects
MH  - Dopamine Antagonists/pharmacology
MH  - Estradiol/pharmacology
MH  - Estriol/pharmacology
MH  - Female
MH  - Genes, Reporter
MH  - Haloperidol/pharmacology
MH  - Herbicides/metabolism/*toxicity
MH  - Humans
MH  - Male
MH  - Mammary Neoplasms, Experimental/*chemically induced
MH  - Ovariectomy
MH  - Prolactin/*blood
MH  - Random Allocation
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptors, Estrogen/antagonists & inhibitors/genetics/metabolism
MH  - Reserpine/pharmacology
MH  - Simazine/metabolism/*toxicity
MH  - Transcriptional Activation
MH  - Triazines/metabolism/*toxicity
MH  - Uterus/drug effects
MH  - Yeasts/genetics/metabolism
EDAT- 2000/11/09 11:00
MHDA- 2001/03/03 10:01
CRDT- 2000/11/09 11:00
PHST- 2000/11/09 11:00 [pubmed]
PHST- 2001/03/03 10:01 [medline]
PHST- 2000/11/09 11:00 [entrez]
AID - 10.1081/dct-100101972 [doi]
PST - ppublish
SO  - Drug Chem Toxicol. 2000 Nov;23(4):575-601. doi: 10.1081/dct-100101972.