690
H O N O R B. FELL A N D L . M. R I N A L D I N I
and mode of action in this respect are still a matter of controversy.
Chvapil and Hurych (1959) and Breslowand Lukens (1960) achieved
hydroxylation of proline in vitro by a system involving ascorbic acid and
hydrogen peroxide, with the possible formation of a free radical, and
Price, working at Robertson's laboratory, could hydroxylate lysine to
hydroxylysine with a similar system. Robertson (1961) put forward the
suggestion that free monodehydroascorbyl and hydroxyl radicals may
take part in collagen synthesis in the living cell.
The role of ASA on the synthesis of mucopolysaccharides of ground
substance is still less clear. The problem has attracted the attention of
several investigators (Penney and Balfour, 1949; Bradfield and Kodicek,
1951; Robertson and Hinds, 1956; Kodicek and Loewi, 1955; Klebanoff, Dziewiatkowski and Okinaka, 1958; Hughes and Kodicek, 1960),
but none of them have used Tissue-Culture methods. A little culture
work has been done, though, on the formation of epithelial cements.
The results of Chambers and Cameron (1943) and of Sacerdote de
Lustig (1944a) in tissue cultures suggest that ASA is not necessary for
the cohesion of epithelial sheets. This is in keeping with the observations
in vivo of Wolbach (1936) and Galloway, Garry and Hitchin (1948) who
found that the healing of epithelial wounds was much less affected by
ASA deprivation than that of cartilage or connective-tissue injuries.
The experiments of Campbell, Ferguson and Garry (1950) and Boyd
and Campbell (1950) on corneal injuries in man and the guinea-pig
show quite clearly that superficial epithelial wounds do not need
ASA for repair but deeper wounds involving the formation of collagen
do.
The whole question of the effect of vitamin C in relation to the building of extracellular materials should be reinvestigated in vitro with
freshly isolated cells still capable of normal differentiation (cf. Rinaldini, 1959) and washed free from non-cellular matter, like those used
by Fitton Jackson (1954) and Fitton Jackson and Smith (1955) for her
important contributions to the electron-microscopy of collagen formation. Cultures of carrageenan granuloma cells could also provide a
very suitable test material.
Finally, it seems possible that vitamin C may not only be concerned
in the building of intercellular materials but also in their breakdown.
The mucolytic activity of ASA was examined by McClean and Hale
(1940, 1941) on mucoprotein from umbilical cord, and by Skanse and
Sundblad (1943) on purified hyaluronic acid. These effects can be
demonstrated with concentrations down to M/3,000 at p H 7-0 with or
without addition of hydrogen peroxide, but it remains to be seen if they
actually occur in tissues.
H O N O R B. FELL A N D L . M. R I N A L D I N I
and mode of action in this respect are still a matter of controversy.
Chvapil and Hurych (1959) and Breslowand Lukens (1960) achieved
hydroxylation of proline in vitro by a system involving ascorbic acid and
hydrogen peroxide, with the possible formation of a free radical, and
Price, working at Robertson's laboratory, could hydroxylate lysine to
hydroxylysine with a similar system. Robertson (1961) put forward the
suggestion that free monodehydroascorbyl and hydroxyl radicals may
take part in collagen synthesis in the living cell.
The role of ASA on the synthesis of mucopolysaccharides of ground
substance is still less clear. The problem has attracted the attention of
several investigators (Penney and Balfour, 1949; Bradfield and Kodicek,
1951; Robertson and Hinds, 1956; Kodicek and Loewi, 1955; Klebanoff, Dziewiatkowski and Okinaka, 1958; Hughes and Kodicek, 1960),
but none of them have used Tissue-Culture methods. A little culture
work has been done, though, on the formation of epithelial cements.
The results of Chambers and Cameron (1943) and of Sacerdote de
Lustig (1944a) in tissue cultures suggest that ASA is not necessary for
the cohesion of epithelial sheets. This is in keeping with the observations
in vivo of Wolbach (1936) and Galloway, Garry and Hitchin (1948) who
found that the healing of epithelial wounds was much less affected by
ASA deprivation than that of cartilage or connective-tissue injuries.
The experiments of Campbell, Ferguson and Garry (1950) and Boyd
and Campbell (1950) on corneal injuries in man and the guinea-pig
show quite clearly that superficial epithelial wounds do not need
ASA for repair but deeper wounds involving the formation of collagen
do.
The whole question of the effect of vitamin C in relation to the building of extracellular materials should be reinvestigated in vitro with
freshly isolated cells still capable of normal differentiation (cf. Rinaldini, 1959) and washed free from non-cellular matter, like those used
by Fitton Jackson (1954) and Fitton Jackson and Smith (1955) for her
important contributions to the electron-microscopy of collagen formation. Cultures of carrageenan granuloma cells could also provide a
very suitable test material.
Finally, it seems possible that vitamin C may not only be concerned
in the building of intercellular materials but also in their breakdown.
The mucolytic activity of ASA was examined by McClean and Hale
(1940, 1941) on mucoprotein from umbilical cord, and by Skanse and
Sundblad (1943) on purified hyaluronic acid. These effects can be
demonstrated with concentrations down to M/3,000 at p H 7-0 with or
without addition of hydrogen peroxide, but it remains to be seen if they
actually occur in tissues.