Reference SummaryChen T, Teratog Carcinog Mutagen 1998;18(3):101-10

Title

 Possible rare involvement of O6-methylguanine formation as a significant mutational factor in mouse urinary bladder carcinogenesis models.

Authors

 Chen T; Yamamoto S; Kitano M; Murai T; Wanibuchi H; Matsukuma S ; Nakatsuru Y ; Ishikawa T ; Fukushima S

Journal

 Teratog Carcinog Mutagen

Volume

 18

Issue

 3

Year

 1998

Pages

 101-10

Abstract

 O-6-methylguanine is known as one of the major premutagenic lesions in the human and rodent carcinogenesis process. O-6-methylguanine-DNA methyltransferase (MGMT), which repairs methylated guanine bases, might prevent the G:C to A:T transition, and transgenic mice carrying this MGMT gene have been reported to be less sensitive to the carcinogenicity of certain alkylating agents. Here we utilized MGMT transgenic mice to assess the significance of O-6-methylguanine formation during urinary bladder carcinogenesis. In experiment 1, 100 and 60 ppm N-butyl-N-(4-hydroxybutyl)nitrosamine was given for 20 weeks to transgenic and non-transgenic mice in their drinking water. The incidences of urinary bladder carcinomas were not different between transgenic mice and non-transgenic mice. The mutational spectrum of the p53 gene was evaluated by polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. The pattern of p53 mutations of transgenic and non-transgenic mice did not differ, and the frequencies of mutations were 40% and 42%, respectively. G:C to A:T transition mutations were particularly infrequent (1 of 14 mutations, 7%). In experiment 2, N- methyl-N-nitrosourea, which might induce O-6-methylguanine in affected alleles, was given once a week, 3 times (total 5 mg) by direct instillation into the urinary bladder through an abdominal incision. No significant neoplastic lesions were detected, although the experiment was limited by severe toxicity of the treatment. P53 immunostaining was done and there was no difference in transgenic and non- transgenic mice. These results suggest that O-6- methylguanine formation might not be a significant mutational factor in these mouse urinary bladder carcinogenesis models. (C) 1998 Wiley-Liss, Inc.

Links

 J:49732 – MGI References
9728794 – National Library of Medicine/PubMed

Strain Notes

Strain Note
C3H/HeN-Tg(MGMT)#Tis The "MGMT" transgene was reported to be highly expressed in the liver and esophagus, and expressed in the bladder of these mice. Little or no expression of the "MGMT" transgene was reported to have been observed in the colon of these mice.

Models
Strain Model Name Treatment Agent(s) Organ Affected Frequency Model Details
C3H/HeN Urinary bladder carcinoma in situ Urinary bladder

0
C3H/HeN-Tg(MGMT)#Tis Urinary bladder carcinoma in situ Urinary bladder

0
C3H/HeN Urinary bladder carcinoma in situ
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

37.5 - 47
C3H/HeN-Tg(MGMT)#Tis Urinary bladder carcinoma in situ
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

17 - 44
C3H/HeN Urinary bladder dysplasia Urinary bladder

0 - 22
C3H/HeN-Tg(MGMT)#Tis Urinary bladder dysplasia Urinary bladder

0 - 14
C3H/HeN Urinary bladder dysplasia
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

65 - 75
C3H/HeN-Tg(MGMT)#Tis Urinary bladder dysplasia
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

39 - 78
C3H/HeN-Tg(MGMT)#Tis Urinary bladder dysplasia
  • N-methyl-N-nitrosourea (MNU)
  • ZnSO4
 Urinary bladder

29 - 60
C3H/HeN Urinary bladder dysplasia
  • N-methyl-N-nitrosourea (MNU)
  • ZnSO4
 Urinary bladder

29 - 100
C3H/HeN Urinary bladder squamous cell carcinoma Urinary bladder

0
C3H/HeN-Tg(MGMT)#Tis Urinary bladder squamous cell carcinoma Urinary bladder

0
C3H/HeN Urinary bladder squamous cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

0 - 44
C3H/HeN-Tg(MGMT)#Tis Urinary bladder squamous cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

5.6 - 50
C3H/HeN Urinary bladder transitional cell carcinoma Urinary bladder

0
C3H/HeN-Tg(MGMT)#Tis Urinary bladder transitional cell carcinoma Urinary bladder

0
C3H/HeN Urinary bladder transitional cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

0 - 62.5
C3H/HeN-Tg(MGMT)#Tis Urinary bladder transitional cell carcinoma
  • N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN)
 Urinary bladder

11 - 44
C3H/HeN-Tg(MGMT)#Tis Urinary bladder transitional cell carcinoma
  • N-methyl-N-nitrosourea (MNU)
  • ZnSO4
 Urinary bladder

0
C3H/HeN Urinary bladder transitional cell carcinoma
  • N-methyl-N-nitrosourea (MNU)
  • ZnSO4
 Urinary bladder

0 - 25