In pseudomonads, naphthalene is catabolized in a series of reactions to salicylic acid, which is further degraded via the catechol meta-cleavage, ortho-cleavage, or gentisic acid pathway to Krebs cycle intermediates. The naphthalene catabolic genes have been located on self-transmissible plasmids, in most cases, and implicated to have chromosomal locations in other cases. The best-studied naphthalene catabolic plasmid is NAH7. It carries two operons, one of which enables the host to utilize naphthalene and the other to utilize salicylate as a carbon and energy source. The product of another NAH7 gene, nahR, is required to turn on both operons in the presence of the inducer, salicylate. Several different naphthalene and salicylate catabolic plasmids have been shown to share sequence homology with NAH7. These plasmids can undergo structural alterations involving insertions and deletions during conjugations and changes in nutritional conditions. Available evidence suggests that salicylate catabolic plasmids can form from the naphthalene catabolic plasmids by structural alterations of the plasmid DNA. The gene organization and regulation, as well as the genetic instability of the naphthalene catabolic plasmids, are reminiscent of the TOL plasmids and suggest that the naphthalene catabolic plasmids and other catabolic plasmids may have evolved in a short period of time by acquiring and modifying preevolved gene clusters from host chromosomes or other plasmids.

KGF is generally well tolerated when administered IV at doses up to 40 microg/kg/d for 3 days before a 5-day course of FU plus leucovorin. A clinically meaningful biologic effect was also suggested in that patients treated with the epithelial growth factor KGF had a lower rate of grade 2 to 4 mucositis than did patients treated with placebo.