Dose-Response Curve

A Genetic Test for Radiation Dose-Response

X-Ray irradiation of a female Drosophila may induce an recessive lethal mutation on one of the two X chromosomes in reproductive cells in her germ line. When mated to an un-irradiated male, some of her daughters will be heterozygous for the chromosome with the recessive lethal (X'X). When these X'X daughters are back-crossed to the un-irradiated hemizygous males (XY), half of the male embryos will inherit the un-mutated maternal X and half will inherit the lethal X'. The latter males die in early development, thus X'X females will have only half the expected proportion of male offspring. The assay for X-linked lethals is the proportion of females with this modified sex ratio.

	X	Y
X'	X' X	X' Y
X	X X	X Y

The graph shows the fraction of lethal mutations induced by various doses of X-Rays (1000 R = 10 Gy). The dose-response curve of X-ray exposure versus rate of induced mutation is linear, which suggests that there is no lower limit (threshold) of radiation exposure that does not produce some mutagenic effect.

Chronic low-level exposure to radiation has been implicated in a variety of medical conditions, including cancer. The estimated slope of the dose-response curve for increased risk of death from cancer is 0.004% per mSv (0.04% per rem).

HOMEWORK: What is the dose-response rate from mutation in Drosophila? Draw the human and Drosophila dose-response curves on the same graph; use a semi-log plot. Discuss the implications for radiation-induced cancer and mutation.