PMID- 10096421
OWN - NLM
STAT- MEDLINE
DCOM- 19990330
LR  - 20190720
IS  - 0304-3835 (Print)
IS  - 0304-3835 (Linking)
VI  - 135
IP  - 2
DP  - 1999 Jan 29
TI  - Enhancement of urinary bladder carcinogenesis in nullizygous p53-deficient mice 
      by N-butyl-N-(4-hydroxybutyl)nitrosamine.
PG  - 137-44
AB  - We recently reported p53 mutations to be frequent in mouse invasive urinary 
      bladder carcinomas, with and without metastasis. However, the role of p53 
      dysfunctions during carcinogenesis remains unclear. In the present study, 
      heterozygous and nullizygous p53-deficient mice and their littermates were 
      treated with the urinary bladder carcinogen, 
      N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN), at a concentration of 0.01% in the 
      drinking water throughout the experiment. This markedly accelerated urinary 
      bladder carcinogenesis but not development of other tumors in the nullizygous 
      p53-deficient mice. Thus the appearance of neoplastic urothelial lesions in 
      nullizygotes (at day 60 of the experiment) was earlier than in wild-type mice and 
      heterozygotes (at day 125). Moreover, malignant vascular tumors (hemangiosarcomas 
      (HS)) were found in all four nullizygotes killed later than day 108. Mutational 
      inactivation of the wild-type allele was not apparent in either the single 
      transitional cell carcinoma observed in a wild-type mouse and a hemangiosarcoma 
      in a heterozygote. Overall, it can be concluded that the number of normal p53 
      alleles is a significant determining factor in the susceptibility of urothelial 
      cells to carcinogens. The role of the p53 defect in mouse urinary bladder 
      carcinogenesis may thus be to diminish the threshold for occurrence of additional 
      genetic alterations.
FAU - Yamamoto, S
AU  - Yamamoto S
AD  - First Department of Pathology, Osaka City University Medical School, Osaka, 
      Japan.
FAU - Min, W
AU  - Min W
FAU - Lee, C C
AU  - Lee CC
FAU - Salim, E I
AU  - Salim EI
FAU - Wanibuchi, H
AU  - Wanibuchi H
FAU - Sukata, T
AU  - Sukata T
FAU - Fukushima, S
AU  - Fukushima S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Ireland
TA  - Cancer Lett
JT  - Cancer letters
JID - 7600053
RN  - 0 (Carcinogens)
RN  - 3817-11-6 (Butylhydroxybutylnitrosamine)
SB  - IM
MH  - Animals
MH  - Butylhydroxybutylnitrosamine
MH  - Carcinogenicity Tests
MH  - Carcinogens
MH  - Carcinoma in Situ/chemically induced/genetics
MH  - Carcinoma, Transitional Cell/chemically induced/genetics
MH  - *Cocarcinogenesis
MH  - Gene Deletion
MH  - Genes, p53/*genetics
MH  - Genotype
MH  - Male
MH  - Mice
MH  - Polymerase Chain Reaction
MH  - Polymorphism, Single-Stranded Conformational
MH  - Urinary Bladder Neoplasms/*chemically induced/*genetics
EDAT- 1999/03/30 00:00
MHDA- 1999/03/30 00:01
CRDT- 1999/03/30 00:00
PHST- 1999/03/30 00:00 [pubmed]
PHST- 1999/03/30 00:01 [medline]
PHST- 1999/03/30 00:00 [entrez]
AID - S0304-3835(98)00288-2 [pii]
AID - 10.1016/s0304-3835(98)00288-2 [doi]
PST - ppublish
SO  - Cancer Lett. 1999 Jan 29;135(2):137-44. doi: 10.1016/s0304-3835(98)00288-2.