Rad. and Environm. Biophys. 12, 253--256 (1975) © by Springer-Verlag 1975
Short Communication
Radiosensitivity and Radiation-Induced Mutability: An Empirical Relationship R. Trujillo and V. L. Dugan Sandia Laboratories Albuquerque, New Mexico, U.S.A, Received May 5, 1975 Summary. The total genome size of various species can apparently define the radiationinduced mutability and radiosensitivity for these species. An empirical expression has been derived which relates the radiation-induced mutation rates of different species to their total DNA content and radiation-induced inactivation r~tes.
Abrahamson et aL [i] have showa t h a t the radiation-induced forward mutation rates for 8 different speeies is proportional to the total genome size (DNA content) of the species. Eq. (t) provides a mathematieal statement of their fmdings: M = ~ wa (1) where M is the mutation rate per locus per rad, w is the nuclear (or genetie) nucleie aeid weight in daltons, and c and d are constants. Their data, excluding the h u m a n mutation rate vMue, together with mutation data for T2 bacteriophage exposed to ionizing radiation were analyzed in terms of Eq. (l) using a least squares norm procedure which provided values for the constants c and d. The results are : M = 5.40 × i0 -~~ w 1.2°s. (2) This funetional expression relates the mutation rate per locus per rad for 8 species, whose mutation rates extend over a range of 6 orders of magnitude, to their nueleie aeid contents, which range in size from i0 s dMtons to t012 daltons. The Spearman r a n k correlation eoefficient of this fit is 0.99596. As pointed out b y Abrahamson et al. [l] the striking proportionality between mutation rate and nueleic aeid weight (Fig. l) for such a wide variety of organisms strongly suggests t h a t extrapolation direetly from experimental organisms to other species can be considered. Kaplan and Moses [8] and Dugan and Trujillo [6] have each proposed a generic expression for the radiation dose required to reduce a surviving population to e -1 of its original p o p u l a t i o n (D37 value). This expression, whieh considers organisms ranging from viruses to mammalian eells, is given b y D37 = a w - õ ,
(3)
where a and b are constants and w is the nueleic acid weight (DNA content) in daltons.
254
R. Trujil]o and V. L. Dugan 9 10-5
10-7
I0"8 o
c::, ~. 10'9
!o'°
10-U
i0q2
,
,
i ,,,,J
I05
107
I08
I09
i0I0
i0i2
i0II
IOB
NUCLEIC ACID MOLECULARWEIGHT (DALTONS)
Fig. 1. Relationship between forward m u t a t i o n rate per locus per rad (@ experimental value, A caIculated value from D3~ values) a n d nuc]eic acid molecular weight. Numbers refer to organisms listed in Table 1, while the straight line represents the fi~ of Eq: (2) to the data using a leas~ squares norm
Table 1. Nucleic Acid C0ntent, lV[utation Rate, and Radiosensitivity of Organisms No.
Organism
DNA Content (Dalton)
Mutation 1Rote (per locus per rad)
Da~ Value ( x 10 a rad)
1.
T2 Phage (Virus)
1.29 x 10 s [6]
1.075 x 10 -i2 [2]
60.98 [2]
2.
E. coli B/r (Bacterium)
7.78 x i09 [1]
i x «0 -s [1]
4.18 [6]
3.
Saccharomyces cerevisiae (Yeast) 1.44 x 10 TM [1]
1.6 x t 0 -9 [t]
4.27 [6] 2.80 [6]
4.
Æeurospora crassa (Fungus)
2.52
10 i° [1]
2.7 x 10 -9 [1]
t4.99 [5]
5.
Drosophila melanogaster (Fruit fly larvae)
1.02 x 10 ii [1] 1.32 x 10 n [1]
1.4 x 10 -8 [I]
2.16 [7]
6.
Ly~op«si~o,~ es~u~~~tu;n
1.i7 × 101~ [q
3.75 x t 0 -~ [1J t.7 x I0 -7 [ t ]
x
t i . 4 9 [3]
(Tomato)
7.
M u s musculus (I~ouse)
1.35
8.
Homo sapiens (Man)
!.7
9.
Hardeum vulgare (Barley)
5.99 x t 0 i2 [1] 6.89 x 10 i2 [1]
x
x
t 0 i2 [~]
0.794 [4] o.õo5 [4]
10 i2 [1] I
x
~0 -ô [t]
0.694 [9]
Radiosensitivity and Mutability Relationship
255
The Ds7 data for the species subjeeted to mutation analysis above were obtained (Table l) and analyzed in terms of Eq. (3) using a least squares norm procedure which provided values for the constants a and b. The results are D37 : 2.458 × ~09 w -°.a576.
(4)
A relationship between radiation-induced mutation and inactivation rates should exist, yielding the following expression M---- 2.t97 × l0 -~9 w 1-565~D3~
(5)
where M is the mutation rate per locus per rad and D37 is radiosensitivity in rads. Eq. (5) indicates t h a t given D37 orte can calculate M if the nucleic acid content of the species being studied is known. The experimental D37 values for the 8 species considered were used to determine a calculated radiation-induced mutation rate using Eq. (5). The results are presented in :Fig. i. Eqs. (2) and (5) both relate mutation rate to the nucleic acid content of biological systems. However, Eq. (2) provides no operational parameter with which to consider the various physiological and enviromnental factors t h a t can influence the experimental determination of radiation-induced mutation rate. Eq. (5) empirically suggests t h a t those physiological and enviromnental factors that influence the survival response (Da7 value) of organisms towards radiation m a y also serve to broadly defme the radiation-induced mutation response of these organisms under the same set of conditions. As shown in Fig. l, a corre]ation coefficient of 0.9846 is obtained between the calculated and experimentally observed mutation rates, particularly when one considers the possible sources of error in experimenta]ly determirdng mutation rate and D37 values. Potential experimental difficulties include the role of repair phenomena among different species; oxygen, temperature and humidity effects influencing radiobiological data; variation in radiosensitivity with species age; variation in radiobio]ogical response with dose rate and type of radiation; and potential difficulties in determining nucleic acid molecular weight. Given these variables it is considered sigaificant t h a t an empirieal relationship between radiation-induced mutability and radiosensitivity has been identified for at least 9 different species. The applicability of such findings to other areas m a s t depend on the generation of applicable data on which to establish whether or not this empirical relationship is generally valid. Acl~nowledgements. The authors are thankful to Dr. Charles A. Trauth, Jr. for the many useful and stimulating discussions pertaining to this paper.
References I. Abrahamson, S., Bender, )/[. A., Conger, A. D., Wolff, S. : Uniformity of radiation-induced mutation rates among different species. Nature (Lond.) 245, 460--463 (i973) 2. Ardashnikov, S. ~., Soyfer, V. ~., Goldfarb, D. M. : Induction of h-mutations in the extracellular phase 12 by y-irradiation. Biochem. biophys. Res. Commun. 16, 455--459 (1964) 3. Brock, R. D., ~ranklin, I. R. : The effect of desiceation, storage, and radiation intensity on mutation rate in tomato pollen. Radiat. Bot. 6, ~171--179 (1966) 4. Casarett, A. P. : In: Radiation biology, p. 220. Englewood Cliffs, New Jersey: Prentice-Hall i968 5. DeSerres, F., Malling, H. V., Webber, B. B. : Dose rate effects on inactivation and mutation induction in Æeurospora crassa A. Brookhaven Symp. Biol. 20, 56--88 (1967)
256
R. Trujillo and V. L. Dugan
6. Dugan, V., Trujillo, R. : On a fundamental problem in radiation biology. J. Theor. Biol. 44, 397--401 (1974) 7. Grosch, D. S. : In: Biological effects of radiation, p. 134. New York: Blaisdell Pub. Comp. 1965 8. Kaplan, It. S., Moses, L. E. : Biological complexity and radiosensitivity. Science 14~, 2t--25 (1964) 9. Mericle, L. W., Mericle, 1%.P.: Radio-sensitivity of developing plant embryos. Brookhaven Symp. Biol. 14, 263--308 (t96t) Dr. R. E. Trujillo Departmen$ 5250 Sandia Laboratories Albuquerque, New Mexico 87115 USA
Short Communication
Radiosensitivity and Radiation-Induced Mutability: An Empirical Relationship R. Trujillo and V. L. Dugan Sandia Laboratories Albuquerque, New Mexico, U.S.A, Received May 5, 1975 Summary. The total genome size of various species can apparently define the radiationinduced mutability and radiosensitivity for these species. An empirical expression has been derived which relates the radiation-induced mutation rates of different species to their total DNA content and radiation-induced inactivation r~tes.
Abrahamson et aL [i] have showa t h a t the radiation-induced forward mutation rates for 8 different speeies is proportional to the total genome size (DNA content) of the species. Eq. (t) provides a mathematieal statement of their fmdings: M = ~ wa (1) where M is the mutation rate per locus per rad, w is the nuclear (or genetie) nucleie aeid weight in daltons, and c and d are constants. Their data, excluding the h u m a n mutation rate vMue, together with mutation data for T2 bacteriophage exposed to ionizing radiation were analyzed in terms of Eq. (l) using a least squares norm procedure which provided values for the constants c and d. The results are : M = 5.40 × i0 -~~ w 1.2°s. (2) This funetional expression relates the mutation rate per locus per rad for 8 species, whose mutation rates extend over a range of 6 orders of magnitude, to their nueleie aeid contents, which range in size from i0 s dMtons to t012 daltons. The Spearman r a n k correlation eoefficient of this fit is 0.99596. As pointed out b y Abrahamson et al. [l] the striking proportionality between mutation rate and nueleic aeid weight (Fig. l) for such a wide variety of organisms strongly suggests t h a t extrapolation direetly from experimental organisms to other species can be considered. Kaplan and Moses [8] and Dugan and Trujillo [6] have each proposed a generic expression for the radiation dose required to reduce a surviving population to e -1 of its original p o p u l a t i o n (D37 value). This expression, whieh considers organisms ranging from viruses to mammalian eells, is given b y D37 = a w - õ ,
(3)
where a and b are constants and w is the nueleic acid weight (DNA content) in daltons.
254
R. Trujil]o and V. L. Dugan 9 10-5
10-7
I0"8 o
c::, ~. 10'9
!o'°
10-U
i0q2
,
,
i ,,,,J
I05
107
I08
I09
i0I0
i0i2
i0II
IOB
NUCLEIC ACID MOLECULARWEIGHT (DALTONS)
Fig. 1. Relationship between forward m u t a t i o n rate per locus per rad (@ experimental value, A caIculated value from D3~ values) a n d nuc]eic acid molecular weight. Numbers refer to organisms listed in Table 1, while the straight line represents the fi~ of Eq: (2) to the data using a leas~ squares norm
Table 1. Nucleic Acid C0ntent, lV[utation Rate, and Radiosensitivity of Organisms No.
Organism
DNA Content (Dalton)
Mutation 1Rote (per locus per rad)
Da~ Value ( x 10 a rad)
1.
T2 Phage (Virus)
1.29 x 10 s [6]
1.075 x 10 -i2 [2]
60.98 [2]
2.
E. coli B/r (Bacterium)
7.78 x i09 [1]
i x «0 -s [1]
4.18 [6]
3.
Saccharomyces cerevisiae (Yeast) 1.44 x 10 TM [1]
1.6 x t 0 -9 [t]
4.27 [6] 2.80 [6]
4.
Æeurospora crassa (Fungus)
2.52
10 i° [1]
2.7 x 10 -9 [1]
t4.99 [5]
5.
Drosophila melanogaster (Fruit fly larvae)
1.02 x 10 ii [1] 1.32 x 10 n [1]
1.4 x 10 -8 [I]
2.16 [7]
6.
Ly~op«si~o,~ es~u~~~tu;n
1.i7 × 101~ [q
3.75 x t 0 -~ [1J t.7 x I0 -7 [ t ]
x
t i . 4 9 [3]
(Tomato)
7.
M u s musculus (I~ouse)
1.35
8.
Homo sapiens (Man)
!.7
9.
Hardeum vulgare (Barley)
5.99 x t 0 i2 [1] 6.89 x 10 i2 [1]
x
x
t 0 i2 [~]
0.794 [4] o.õo5 [4]
10 i2 [1] I
x
~0 -ô [t]
0.694 [9]
Radiosensitivity and Mutability Relationship
255
The Ds7 data for the species subjeeted to mutation analysis above were obtained (Table l) and analyzed in terms of Eq. (3) using a least squares norm procedure which provided values for the constants a and b. The results are D37 : 2.458 × ~09 w -°.a576.
(4)
A relationship between radiation-induced mutation and inactivation rates should exist, yielding the following expression M---- 2.t97 × l0 -~9 w 1-565~D3~
(5)
where M is the mutation rate per locus per rad and D37 is radiosensitivity in rads. Eq. (5) indicates t h a t given D37 orte can calculate M if the nucleic acid content of the species being studied is known. The experimental D37 values for the 8 species considered were used to determine a calculated radiation-induced mutation rate using Eq. (5). The results are presented in :Fig. i. Eqs. (2) and (5) both relate mutation rate to the nucleic acid content of biological systems. However, Eq. (2) provides no operational parameter with which to consider the various physiological and enviromnental factors t h a t can influence the experimental determination of radiation-induced mutation rate. Eq. (5) empirically suggests t h a t those physiological and enviromnental factors that influence the survival response (Da7 value) of organisms towards radiation m a y also serve to broadly defme the radiation-induced mutation response of these organisms under the same set of conditions. As shown in Fig. l, a corre]ation coefficient of 0.9846 is obtained between the calculated and experimentally observed mutation rates, particularly when one considers the possible sources of error in experimenta]ly determirdng mutation rate and D37 values. Potential experimental difficulties include the role of repair phenomena among different species; oxygen, temperature and humidity effects influencing radiobiological data; variation in radiosensitivity with species age; variation in radiobio]ogical response with dose rate and type of radiation; and potential difficulties in determining nucleic acid molecular weight. Given these variables it is considered sigaificant t h a t an empirieal relationship between radiation-induced mutability and radiosensitivity has been identified for at least 9 different species. The applicability of such findings to other areas m a s t depend on the generation of applicable data on which to establish whether or not this empirical relationship is generally valid. Acl~nowledgements. The authors are thankful to Dr. Charles A. Trauth, Jr. for the many useful and stimulating discussions pertaining to this paper.
References I. Abrahamson, S., Bender, )/[. A., Conger, A. D., Wolff, S. : Uniformity of radiation-induced mutation rates among different species. Nature (Lond.) 245, 460--463 (i973) 2. Ardashnikov, S. ~., Soyfer, V. ~., Goldfarb, D. M. : Induction of h-mutations in the extracellular phase 12 by y-irradiation. Biochem. biophys. Res. Commun. 16, 455--459 (1964) 3. Brock, R. D., ~ranklin, I. R. : The effect of desiceation, storage, and radiation intensity on mutation rate in tomato pollen. Radiat. Bot. 6, ~171--179 (1966) 4. Casarett, A. P. : In: Radiation biology, p. 220. Englewood Cliffs, New Jersey: Prentice-Hall i968 5. DeSerres, F., Malling, H. V., Webber, B. B. : Dose rate effects on inactivation and mutation induction in Æeurospora crassa A. Brookhaven Symp. Biol. 20, 56--88 (1967)
256
R. Trujillo and V. L. Dugan
6. Dugan, V., Trujillo, R. : On a fundamental problem in radiation biology. J. Theor. Biol. 44, 397--401 (1974) 7. Grosch, D. S. : In: Biological effects of radiation, p. 134. New York: Blaisdell Pub. Comp. 1965 8. Kaplan, It. S., Moses, L. E. : Biological complexity and radiosensitivity. Science 14~, 2t--25 (1964) 9. Mericle, L. W., Mericle, 1%.P.: Radio-sensitivity of developing plant embryos. Brookhaven Symp. Biol. 14, 263--308 (t96t) Dr. R. E. Trujillo Departmen$ 5250 Sandia Laboratories Albuquerque, New Mexico 87115 USA
