@entity11517 ( @entity11517 ) point mutations are induced by XXXX in @entity19 oral squamous epithelia, @entity957 and loss of heterozygosity occur without additional exposure.

@entity1978 @entity11517 @entity5 @entity19 @entity957 @entity189 @entity1613 @entity105 @entity6349 @entity1141
Tumorigenesis is a multistep genetic process requiring several somatic mutations for @entity5 . These mutations appear to be sequential, random, and independent events. However, we find linked, nonrandom ras mutations occurring during @entity1978 -induced @entity105 months after exposure to the carcinogen had ceased. The carcinogen had been topically applied to the oral cavity of CBA @entity19 for 4 to 16 weeks. @entity1141 developed after 24 weeks, and @entity189 in situ and @entity957 developed after 28 weeks. @entity11517 mutations were detected in 13 of 25 tissue specimens (10 of 14 invasive @entity189 in situ, 1 of 5 @entity6349 tissue, and 0 of 2 normal tissues). Approximately one-half of the @entity5 had G to A point mutations at codon 12 of the cellular @entity11517 proto-oncogene on @entity19 chromosome 7. None had codon 11, 13, or 61 mutations. Loss of heterozygosity occurred in 5 of 14 invasive @entity5 . @entity957 consistently lost the wild-type allele, whereas @entity1613 and small @entity5 were heterozygous for ras. This suggests a causal relationship between carcinogen treatment, @entity11517 activation, and initiation of @entity105 . The wild-type allele in @entity19 chromosome 7 is lost with the progression of @entity105 long after exposure to the carcinogen. Thus, loss of heterozygosity of the ras gene appears to occur without multiple carcinogen-induced mutations, i.e., as a result of a cascade of events induced by an earlier ras mutation.
