TABLE 4-3B Dominant Visible Mutations Recovered in the Course of Mouse Specific Locus Experiments (Spermatogonial Irradiation)

Expt No.

X-ray Dose (Gy)

Number of Progeny

Number of mutations at

Mutations per Locus per Gray (× 105)

Reference

Sl

W

Sp

T

Total

1

6 + 6 (8-week interval)

3,612

1

1

0.58a

Lyon and others (1964)

2

6

16,735

1

1

0.25

Lyon and Morris (1969)

3

5 + 5

7,168

1

1

0.35a

Cattanach and Moseley (1974)

Cattanach and others (1985)

4

3 + 3

7,645

2

2

1.09a

Cattanach and Rasberry (1994)

Cattanach and others (1985)

5

3 + 3

15,849

1

1

1

3

6

0.35b

Cattanach and Rasberry (1994)

Cattanach and others (1985)

6

6

10,897

1

1

0.38

Cattanach and Rasberry (1994)

7

6

19,285

1

1

0.22

Cattanach and Rasberry (1994)

8

1 + 9

10,318

1

1

2

0.24a

Cattanach and others (1985)

9

1 + 9

14,980

3

3

0.50a

Cattanach and others (1985)

Unweighted average: 3.96/9 = 0.44 per locus per gray

NOTE: Experiments were carried out during 1964–1994 in Harwell, England. All rates are normalized to single acute X-irradiation conditions.

aNormalized to single unfractionated irradiation conditions under the assumption of additivity of yields.

bNormalized to single unfractionated irradiation (by dividing the rate by 3) on the basis of observations of the enhancement of specific locus mutation frequency (in the same experiment by a factor of 3 [3H1 strain of mice]).

The committee therefore used the following approach to derive the average induced rate of mutations. All experimental data were first grouped by loci, so that an unweighted estimate of the locus-specific induced rates could be derived from the average of the estimates from all experiments involving each of the loci. Subsequently, these locus-specific rates were averaged across loci to arrive at the average induced mutation rate. This procedure permitted calculation of the standard error of the estimated rate that incorporated the sampling variability across loci as well as the variability of the rates in individual experiments. In this approach, unpublished data of Neel and Lewis (1990) were excluded since details of the identity of all the loci and the loci at which mutations were recovered were unavailable. Although fewer data were used (the total number of loci became 34), this approach was considered preferable since (1) no locus is double-counted while averaging over all loci, (2) the loci and the corresponding mutant phenotypes are clear, and (3) an estimate of the standard error of the mean (which takes into account both intra- and interlocus variability) can be given. These data permit an overall average estimate of (1.08 ± 0.30) × 10−5 per locus per gray (Table 4-3C). With a dose-rate reduction factor of 3 traditionally used1 (Russel 1965;

1  

In the mouse, the dose-rate reduction factor of 3 for spermatogonial irradiations comes not only from the 6 Gy data of Dr. William Russell but also from the analysis of Dr. Tony Searle published in the Proceedings of the Cortina International Radiation Reseach Conference in 1967. Dr. Searle analyzed all of the chronic radiation data in the range from 37.5 to 861 R statistically and showed that the exposure-frequency relationship is linear and that the straight line of best fit could be described by

Y = 8.34 x 10−6 + 6.59 x 10−8X,

where Y is the yield of mutations and X is the exposure in roentgens. The slope is one-third of that for acute X-irradiation (300 and 600 R).

Further, the following statement from BEIR V (NRC 1990, p. 110) provides additional substantiation for the dose-rate reduction factor of 3: “The other important baseline value for spermatogonia is for the response to low dose-rate, low-LET irradiations … the rate is (7.3 ± 0.8)10−8/locus/rad for total doses between 35 and 900 rad (Ru82a). The dose-rate factor is 3.0 ± 0.4.”



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