IMPACT OF HELICOBACTER-HEPATICUS INFECTION IN B6C3F(1) MICE FROM 12 NATIONAL TOXICOLOGY PROGRAM 2-YEAR CARCINOGENESIS STUDIES

Male and female B6C3F(1) mice from 12 National Toxicology Program (NTP ) 2-yr carcinogenesis studies were found to be infected with Helicobac ter hepaticus. Many of the male mice from 9 of these studies had an as sociated hepatitis (affected studies). Helicobacter hepaticus has been reported to be associated with an increased incidence of hepatitis an d hepatocellular neoplasms in the A/JCr male mouse. We attempted to de termine if the data from the Helicobacter-affected NTP B6C3F(1) mouse studies were compromised and unsuitable for cancer hazard identificati on. The incidences of neoplasms of the liver (both hepatocellular and hemangiosarcoma) but not of other organs in control male B6C3F(1) mice were increased in affected studies as compared with control males fro m unaffected studies. The increased incidence of hepatocellular neopla sms was observed in those males exhibiting H. hepaticus-associated hep atitis. Other observations further differentiated control male mice fr om affected and unaffected studies. H-ras codon 61 CAA to AAA mutation s were less common in liver neoplasms from males from affected studies as compared with historical and study controls. Tn addition, increase s in cell proliferation rates and apoptosis were observed in the liver s of male mice with H. hepaticus-associated hepatitis. These data supp ort the hypothesis that the increased incidence of liver neoplasms is associated with H. hepaticus and that hepatitis may be important in th e pathogenesis. Therefore, interpretation of carcinogenic effects in t he liver of B6C3F(1) mice may be confounded if there is H. hepaticus-a ssociated hepatitis.