Carcinogenicity of XXXX in @entity899 heterozygous knockout and wild-type C57BL/6J @entity19 .

@entity1 @entity3496 @entity35 @entity706 @entity5 @entity899 @entity19 @entity242 @entity3495 @entity3494
There is abundant epidemiological evidence that @entity3494 is an environmental carcinogen related to @entity1 @entity5 of the skin, lung, liver and urinary bladder, in particular. @entity3495 ( @entity3496 ) has also been reported to act as a carcinogen/or a promoter in @entity35 models. To elucidate molecular mechanisms, we conducted an 18 month carcinogenicity study of @entity3496 in @entity899 heterozygous (+/-) knockout @entity19 , which are susceptible to early spontaneous development of various types of @entity5 , and wild-type (+/+) C57BL/6J @entity19 . Totals of 88-90 males, 7-8 weeks of age, were divided into three groups each administered 0, 50 or 200 p.p.m. @entity3496 in their drinking water for 18 months. @entity19 that were found moribund or died before the end of the study were autopsied to evaluate the @entity5 induction levels, as well as those killed at the end. Both @entity899 (+/-) knockout and wild-type @entity19 demonstrated spontaneous @entity5 development, but lesions were more prevalent in the knockout case. Carcinogenic effect of @entity3496 was evident by significant early induction of @entity5 in both treated @entity899 (+/-) knockout and wild-type @entity19 , significant increase of the @entity5 multiplicity in 200 p.p.m.-treated @entity899 (+/-) knockout @entity19 , and by significant increase in the incidence and @entity5 ( @entity706 ) in the treated wild-type @entity19 . By the end of 80 weeks, @entity5 induction, particularly @entity706 and @entity242 , were similar in treated and control @entity899 (+/-) knockout @entity19 . No evidence for organ- @entity5 specificity of @entity3496 was obtained. Molecular analysis using PCR-SSCP techniques revealed no @entity899 mutations in lymphomas from either @entity899 (+/-) knockout or wild-type @entity19 . In conclusion, @entity3496 primarily exerted its carcinogenic effect on spontaneous development of @entity5 with both of the animal genotypes investigated here.
