Measurement of HPRT mutant frequencies in T-lymphocytes from healthy human populations.
Somatic cell mutant frequencies at the hprt locus of the X-chromosome were measured with the T-lymphocyte cloning technique in healthy human populations. A statistical analysis was performed of assays from 232 individuals (77 males and 155 females) ranging in age from 19 to 80 years. Data from 4 donor groups were compiled: (a) 132 participants in a study of identical and fraternal twins; (b) 17 health care workers studied as part of an assessment of the risks of handling chemotherapeutic drugs; (c) 62 women with benign breast masses; and (d) 21 normal laboratory and office personnel. The relationship between age and mutant frequency (MF) was expressed by the equation: ln MF = 1.46 + 0.018 age (P < 0.001). Thus, MF increased by about 2% per year. Increases in cloning efficiency (CE) reduced the MF, as shown in the equation: ln MF = 2.91 - 1.32 CE (P < 0.001). CE was significantly related to age (CE = 0.47 - 0.002 age, P = 0.038), and the interdependent relationship between MF, age and CE expressed by the equation: ln MF = 1.99 - 1.13 CE + 0.016 age was significant at the P < 0.001 level. There was no statistically significant effect of donor gender or smoking history on MF in our population, but CE was significantly lower in males (P < 0.001). These findings confirm the importance of age and CE as factors which influence the thioguanine-resistant MF in circulating T-lymphocytes from normal adults.
Branda
R F
RF
Genetics Laboratory, Vermont Cancer Center, Burlington 05401.
Sullivan
L M
LM
O'Neill
J P
JP
Falta
M T
MT
Nicklas
J A
JA
Hirsch
B
B
Vacek
P M
PM
Albertini
R J
RJ
D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D002999:Clone Cells; D005260:Female; D006801:Humans; D007041:Hypoxanthine Phosphoribosyltransferase / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009154:Mutation; D012737:Sex Factors; D012907:Smoking; D013223:Statistics as Topic; D013601:T-Lymphocytes / Q000378:metabolism*; D014429:Twins, Dizygotic
D007041:Hypoxanthine Phosphoribosyltransferase