Hereditas 87:151-154 (1977)
Chromosome breaks in Werner’s syndrome and their prevention in vitro by radical-scavenging enzymes I . NORDENSON Department of Medical Genetics, University of Umed, Sweden
NORDENSON,I. 1977. Chromosome breaks in Werner’s syndrome and their prevention in vitro by radical-scavenging enzymes. - Hereditas 87:151-154. Lund, Sweden. ISSN 0018-0661. Received July 12, 1977 An increased frequency of chromosome aberrations was found in cultured lymphocytes from four patients with Werner’s syndrome. Addition of the enzymes superoxide dismutase and catalase to the cultures decreased the frequency of chromosome breaks. Ingrid Nordenson, Department of Medical Genetics, University of Umed, S-90187 Umed, Sweden
Werner’s syndrome is a rare, autosomal recessive disease, characterised by precocious ageing. The patients have a senile appearance with early graying of the hair, short stature, cataracts, loss of sub-cutaneous fat and early arteriosclerosis. The average life span is 47 years and 10% of the patients develop neoplasms (MARTIN et al. 1970). Normal ageing is a complex process influenced by a number of factors of which some appear to be genetic. Studies of diseases like Werner’s syndrome may help to elucidate the genetics of ageing. When living organisms are irradiated, free radicals are produced. As such irradiation also causes symptoms of ageing, it has been suggested that free radicals, arising in the living organisms through the interaction of oxygen and oxidation enzymes, may be involved in the ageing processes 1954). Free radicals may also, indirectly (HARMAN or directly, cause chromosome aberrations and cancer. The frequency of chromosome aberrations have been found to increase with age in both man and other mammals (STEVENSON and
1961 ; MATCEVI and SALZANO 1976). FurtherCURTIS more X-rays have been found to cause a higher frequency of chromosome aberrations in old mice compared with young ones. In view of these relationships between ageing, chromosome aberrations and cancer it was deemed to be of interrest to examine naturally occurring chromosome aberrations in patients with Werner’s syndrome. We have also studied the effects of the enzymes superoxide dismutase (SOD) and cataiase, which have been shown to decrease the frequency of both spontaneously occurring chromosome breaks in Fanconi’s 1977) and radiation-induced anemia (NORDENSON breaks (NORDENSON et al. 1976).
Material and methods Lymphocyte cultures from peripheral blood were (1966) with slight set up according to HUNGERFORD modifications. Culture medium was Parker 199
I52
Hereditas 8 7 (1977)
I. NORDENSON
Table 1. Chromosomal aberrations in four patients with Werner's syndrome and controls Patients T.S. and J.S. were examined on two different occasions (a and b) Aberrations Gaps
Patients A.S. T.S. a b J.S. a b (3.0. Controls
Chromatid Chrcmosome
6
7 7 7 4 5 7
6
0
13 12 11 11 12
AU
28 30
24 22 21 25 8
Tuhle 2 . Effects of superoxide dismutase and catalase (0.05 mglml medium) on the frequency of spontaneously occurring chromosomal aberrations in four patients with Werner's syndrome Treatment of cells
No. ofcellsanalysed No. of Gaps Chromatid aberrations Chromosome aberrations AU aberrations
None
SOD
Catalase SODand catalase
450
450
450
42
30
32
IS**
38
21'
19**
16**
lo** 61***
62***
25 105
11"
No. of Aberrations No. of ceUs with percell cells aberrations analyzed
21 20 20 16
15 19 5
0.28
100
0.30
100 100 100 100 150 3M)
0.24 0.22 0.21 0.13 0.02
according to the WHO recommendations (BUCKand EVANS1973). At least 100 cells were analysed in each person. Four patients, of which 3 were brothers, were examined. The patients were 49, 47, 43 and 36 years old. Controls were lymphocyte cultures from three normal persons, matched for sex and age (31-51 years).
TON
450
12'
&***
Difference from controls * P
Chromosome breaks in Werner’s syndrome and their prevention in vitro by radical-scavenging enzymes I . NORDENSON Department of Medical Genetics, University of Umed, Sweden
NORDENSON,I. 1977. Chromosome breaks in Werner’s syndrome and their prevention in vitro by radical-scavenging enzymes. - Hereditas 87:151-154. Lund, Sweden. ISSN 0018-0661. Received July 12, 1977 An increased frequency of chromosome aberrations was found in cultured lymphocytes from four patients with Werner’s syndrome. Addition of the enzymes superoxide dismutase and catalase to the cultures decreased the frequency of chromosome breaks. Ingrid Nordenson, Department of Medical Genetics, University of Umed, S-90187 Umed, Sweden
Werner’s syndrome is a rare, autosomal recessive disease, characterised by precocious ageing. The patients have a senile appearance with early graying of the hair, short stature, cataracts, loss of sub-cutaneous fat and early arteriosclerosis. The average life span is 47 years and 10% of the patients develop neoplasms (MARTIN et al. 1970). Normal ageing is a complex process influenced by a number of factors of which some appear to be genetic. Studies of diseases like Werner’s syndrome may help to elucidate the genetics of ageing. When living organisms are irradiated, free radicals are produced. As such irradiation also causes symptoms of ageing, it has been suggested that free radicals, arising in the living organisms through the interaction of oxygen and oxidation enzymes, may be involved in the ageing processes 1954). Free radicals may also, indirectly (HARMAN or directly, cause chromosome aberrations and cancer. The frequency of chromosome aberrations have been found to increase with age in both man and other mammals (STEVENSON and
1961 ; MATCEVI and SALZANO 1976). FurtherCURTIS more X-rays have been found to cause a higher frequency of chromosome aberrations in old mice compared with young ones. In view of these relationships between ageing, chromosome aberrations and cancer it was deemed to be of interrest to examine naturally occurring chromosome aberrations in patients with Werner’s syndrome. We have also studied the effects of the enzymes superoxide dismutase (SOD) and cataiase, which have been shown to decrease the frequency of both spontaneously occurring chromosome breaks in Fanconi’s 1977) and radiation-induced anemia (NORDENSON breaks (NORDENSON et al. 1976).
Material and methods Lymphocyte cultures from peripheral blood were (1966) with slight set up according to HUNGERFORD modifications. Culture medium was Parker 199
I52
Hereditas 8 7 (1977)
I. NORDENSON
Table 1. Chromosomal aberrations in four patients with Werner's syndrome and controls Patients T.S. and J.S. were examined on two different occasions (a and b) Aberrations Gaps
Patients A.S. T.S. a b J.S. a b (3.0. Controls
Chromatid Chrcmosome
6
7 7 7 4 5 7
6
0
13 12 11 11 12
AU
28 30
24 22 21 25 8
Tuhle 2 . Effects of superoxide dismutase and catalase (0.05 mglml medium) on the frequency of spontaneously occurring chromosomal aberrations in four patients with Werner's syndrome Treatment of cells
No. ofcellsanalysed No. of Gaps Chromatid aberrations Chromosome aberrations AU aberrations
None
SOD
Catalase SODand catalase
450
450
450
42
30
32
IS**
38
21'
19**
16**
lo** 61***
62***
25 105
11"
No. of Aberrations No. of ceUs with percell cells aberrations analyzed
21 20 20 16
15 19 5
0.28
100
0.30
100 100 100 100 150 3M)
0.24 0.22 0.21 0.13 0.02
according to the WHO recommendations (BUCKand EVANS1973). At least 100 cells were analysed in each person. Four patients, of which 3 were brothers, were examined. The patients were 49, 47, 43 and 36 years old. Controls were lymphocyte cultures from three normal persons, matched for sex and age (31-51 years).
TON
450
12'
&***
Difference from controls * P
