PMID- 10076560
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190513
IS  - 0910-5050 (Print)
IS  - 1876-4673 (Electronic)
IS  - 0910-5050 (Linking)
VI  - 90
IP  - 1
DP  - 1999 Jan
TI  - Promotion by sodium L-ascorbate in rat two-stage urinary bladder carcinogenesis 
      is dependent on the interval of administration.
PG  - 16-22
AB  - In our two-stage model of rat urinary bladder carcinogenesis employing 
      N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) as the initiator, sodium L-ascorbate 
      (Na-AsA) exhibits dose-dependent promotion. In the present study, in order to 
      assess the possible reversibility of the promoting effects, we investigated how 
      different administration periods of Na-AsA influence its promoting activity. In 
      experiment 1, rats were treated with 5% Na-AsA for different administration 
      periods with or without withdrawal and injected with 5-bromo-2'-deoxyuridine 
      (BrdU) to allow determination of the cell proliferation status. Replicative DNA 
      synthesis in the urinary bladder epithelium was shown to return to normal after 
      removal of the promoting stimulus. In experiment 2, rats were initially given BBN 
      for 4 weeks and subsequently received 16 weeks of Na-AsA, alternating with basal 
      diet, at intervals of 4, 8 or 16 weeks, within a total 32-week period. The longer 
      the continuous exposure to Na-AsA, the greater the yield of papillomas and 
      carcinomas in the urinary bladder. In experiment 3, Na-AsA was given for 4 or 8 
      weeks after BBN initiation and the animals were killed at weeks 8 and 12. Both 
      promotion of lesion development and increase of DNA synthesis in the urinary 
      bladder epithelium were dependent on the length of exposure to Na-AsA and the 
      total period of exposure. The results indicate that the promoting effects of 
      Na-AsA in urinary bladder carcinogenesis are reversible to a certain extent after 
      its withdrawal, and the existence of a cumulative exposure time threshold seems 
      likely.
FAU - Chen, T X
AU  - Chen TX
AD  - First Department of Pathology, Osaka City University Medical School.
FAU - Wanibuchi, H
AU  - Wanibuchi H
FAU - Murai, T
AU  - Murai T
FAU - Kitano, M
AU  - Kitano M
FAU - Yamamoto, S
AU  - Yamamoto S
FAU - Fukushima, S
AU  - Fukushima S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Japan
TA  - Jpn J Cancer Res
JT  - Japanese journal of cancer research : Gann
JID - 8509412
RN  - 0 (Carcinogens)
RN  - 3817-11-6 (Butylhydroxybutylnitrosamine)
RN  - G34N38R2N1 (Bromodeoxyuridine)
RN  - PQ6CK8PD0R (Ascorbic Acid)
SB  - IM
MH  - Animals
MH  - Ascorbic Acid/*toxicity
MH  - Bromodeoxyuridine
MH  - Butylhydroxybutylnitrosamine/*toxicity
MH  - Carcinogens/*toxicity
MH  - Carcinoma/chemically induced/pathology
MH  - Drug Administration Schedule
MH  - Hyperplasia
MH  - Male
MH  - Papilloma/chemically induced/pathology
MH  - Rats
MH  - Rats, Inbred F344
MH  - Time Factors
MH  - Urinary Bladder/*drug effects/pathology
MH  - Urinary Bladder Neoplasms/*chemically induced/pathology
PMC - PMC5925984
EDAT- 1999/03/17 00:00
MHDA- 1999/03/17 00:01
PMCR- 1999/01/01
CRDT- 1999/03/17 00:00
PHST- 1999/03/17 00:00 [pubmed]
PHST- 1999/03/17 00:01 [medline]
PHST- 1999/03/17 00:00 [entrez]
PHST- 1999/01/01 00:00 [pmc-release]
AID - S0910505099800222 [pii]
AID - CAE16 [pii]
AID - 10.1111/j.1349-7006.1999.tb00660.x [doi]
PST - ppublish
SO  - Jpn J Cancer Res. 1999 Jan;90(1):16-22. doi: 10.1111/j.1349-7006.1999.tb00660.x.