In CRC, the methylation status of multiple promoters can be predicted through knowledge of BRAF and, to a lesser extent, KRAS activating mutations, indicating that these mutations are closely associated with different patterns of DNA hypermethylation. These changes may be important events in colorectal tumorigenesis.

No abstract

Antibiotic resistances of two sets of SdlnIOnelld typhimurium rfd transductants (along with those of their smooth pyrE+ and c p E + sister transductants) were measured. One set was derived from a pyrE smooth L T~ parent and the other from a cysE smooth LT7 parent. Results showed that strains with defects at the rfa(R-res-2) level and deeper were more susceptible to bacitracin, novobiocin and polymyxin. Those with defects at the rfdG level or deeper were in addition more sensitive to vancomycin, erythromycin, oxacillin and nafcillin. At these levels the presence or abse.nce of galactose I or glucose I from the lipopolysaccharide core made a considerable difference. A heptose-less rfaE mutant was the most sensitive of the strains tested to the above named antibiotics. Strains with rfa lesions at several levels of defect showed slight increases in resistances to tetracycline, cephalothin, ampicillin and penicillin.One would expect strains with gdlE mutations to be similar to rfa(R-res-2) strains and ' those with galU mutations to be similar to rfaG strains if the core defects accounted for the differing antibiotic resistances. They proved to be so except that the galE and gdlu strains in the S. typhimurium FIRN line were as resistant to novobiocin as were smooth strains. The results are interpreted in respect to Nikaido's hypothesis that hydrophilic antibiotics with molecular weights of less than about 650 can gain access to the periplasmic space through protein-lined, water-filled pores and that hydrophobic ones can gain access in deep rough strains when phospholipid patches appear on the surface due to absence of polysaccharides and proteins.

Our results appear to indicate that exposure to A-bomb radiation has caused significant increases in inflammatory activity that are still demonstrable in the blood of A-bomb survivors and which may lead to increased risks of cardiovascular disease and other non-cancer diseases.

S U M M A R YSeveral mutants obtained from smooth SalmoneIla typhimurium strains by selection for resistance to Felix 0 (FO) phage [whose receptor site includes the N-acetylglucosamine branch of the lipopolysaccharide (LPS) core] were smooth in cultural properties, antigenic character and phage sensitivity pattern (except for their FO resistance). However, the affected genes of several such 'FOR' (FOresistant) mutants were shown by transduction to map in the short cysE-pyrE segment, which includes nearly all known rfa genes responsible for synthesis of LPS core. All of seven FOR mutants differed from their parents, and resembled rfa mutants with defects in the deeper part of the LPS core, by increased sensitivity to various antibiotics. One FOR mutant was non-virulent (LD,, > 107, compared with < IOO for its parent); L T~ derivatives given this FOR gene by co-transduction with cysE+ were likewise non-virulent. It is inferred that FOR mutations affect the assembly of the inner part of the LPS core, perhaps causing incomplete blocks in glycosyl transferase reactions. I N T R O D U C T I O NFelix 0 phage (hereinafter called FO) attacks nearly all smooth strains of Salmonella, whatever their 0 antigen, but is active on very few strains of Escherichia coli, etc. (Kallings, 1967). In Salmonella typhimurium it attacks not only smooth strains but also some nonsmooth mutants: those unable to transfer 0 chains from their site of synthesis to the 'complete' lipopolysaccharide (LPS) core, through mutation at rfaL or rfbT; the semirough (SR) class rfc, deficient in polymerization of 0 repeating units; and classes rfb and ymi, unable to synthesize 0 repeating units (Wilkinson, Gemski & Stocker, 1972). Phage FO, however, does not attack rfa mutants of various classes in which synthesis of the LPS core is defective. Lindberg and his colleagues (for review see Lindberg, 1973), from host range and from measurements of rates of adsorption by whole bacteria and of neutralization by isolated LPS, infer that the N-acetylglucosamine side-branch which is attached to the glucose I1 unit of the complete LPS core (Fig. I ) is an essential part of the adsorption site of FO phage. Most mutants selected from smooth strains by application of FO phage are of type [fa, with various sorts of defects in LPS core structure, and are recognizable as such by sensitivity to different combinations of rough-specific phages and/or to bile salts and by total or partial loss of 'smooth' cultural characters, 0 antigen(s) and sensitivity to smoothspecific phages (Wilkinson et a/. 1972). We here describe FO-resistant mutants of smooth * Present address :